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Background Cancer has always been a serious health threat for human. Patients with cancer are at high risk of drug-related problems (DRPs) due to multi-morbidity associated polypharmacy. However, data is lacking in identifying and addressing potential DRPs in cancer patients in China. This study aims to investigate the prevalence of DRPs and evaluate the effectiveness of an independent anti-neoplastic medication therapy management (MTM) system in ambulatory cancer patients. Methods This is a retrospective study. An independent anti-neoplastic MTM system in Shanghai Jiao Tong University affiliated sixth People's Hospital was established in 2018 with the collaboration of oncologists, clinical pharmacists and software engineers. The system contains an independent clinic of pharmacy and MTM software. The software consisted of six modules to help clinical pharmacists serve the tumor patients. The six modules include medication therapy review, intervention plan, personal medication record, medication-related action plan, intervention and/or referral, and documentation and follow-up. Results A total of 173 eligible tumor patients visited the anti-neoplastic pharmaceutical clinic and were recorded in the independent anti-neoplastic MTM system from Jun 2018 to May 2019. The average clinic visits were 2.4 times of the study participants. Two thirds patients (117/173) had one or more identified DRPs in medication therapy review. Adverse drug reaction, potential drug interaction and non-adherence were the leading DRPs. 85.8% of DRPs could be resolved (cured or improved) in four weeks. Tumor patients showed medication adherence reached 84–100% after three or four times of follow-up and intervention. Conclusions The participation of clinical pharmacists in managing polypharmacy tumor patients, with the independent anti-neoplastic MTM system, facilitated the identifying and solving DRPs, especially improving medication adherence of patients, and thus enhancing the effectiveness, safety and rational use of medication.

Two new 5,10b-ethanophenanthridine bridge alkaloids, 3-O-methyl–epi–vittatine, 1, and crouchinine, 2, (2R)-7-hydroxyflavan, 3, and a novel ceramide, brunsceramide, were isolated from the bulbs of Brunsvigia natalensis. (2R)-7-Hydroxyflavan showed total growth inhibition in the 55–60 ppm range against the melanoma (UACC62), breast (MCF7) and renal (TK10) cancer cell lines. 3-O-Methyl–epi–vittatine, 1, and bruns-ceramide, 4, were inactive against the cell lines tested.

Breast cancer patients use numerous medications, which include cytotoxic chemotherapy drugs, hormonal agents and supportive medication, so they are more vulnerable to potential adverse drug interactions. This study aimed to evaluate frequency, severity, clinical importance and risk factors responsible for the Drug-drug interactions (DDIs) in a cohort of patients suffering from breast cancer. Data was obtained from 150 patients in the oncology ward (both inpatient and outpatient) with a confirmed diagnosis of breast cancer and currently receiving standard breast cancer-directed treatment. The data was recorded into a pre-designed form specifically made for this study through individual patient interviews and by reviewing the detailed medical chart records of the patients. DDIs were identified by using drug interaction software such as Medscape mobile application and Micromedex version 2. The results of this study showed that all patients were female. The mean numbers of drugs that patients used were 7. Potential drug interactions were identified in 92% of the patients. When drug groups were overviewed, 32% of interactions were between anti neoplastic drugs, 62.9% interactions were between the anti neoplastic agent and supportive care drugs and 5% of them were between anti-cancer drugs and drugs used to treat comorbidities. Major DDIs were found in 62.2% of patients, 25.3% of DDIs were moderate and 12.4% were minor. The number of drugs, comorbid diseases, and selection of chemo protocols were the risk factors for drug interactions. Most of the DDIs found in breast cancer therapy may have adverse consequences on patient health and therapeutic outcomes. Therefore, health care professionals should review the medication regimen of patients with breast cancer before starting any chemotherapy treatment.

Abstract: Phytochemicals are being used for thousands of years to prevent dreadful malignancy. Side effects of existing allopathic treatment have also initiated intense research in the field of bioactive phytochemicals. Gallic acid, a natural polyphenolic compound, exists freely as well as in polymeric forms. The anti-cancer properties of gallic acid are indomitable by a variety of cellular pathways such as induction of programmed cell death, cell cycle apprehension, reticence of vasculature and tumor migration, and inflammation. Furthermore, gallic acid is found to show synergism with other existing chemotherapeutic drugs. Therefore, the antineoplastic role of gallic acid suggests its promising therapeutic candidature in the near future. The present review describes all these aspects of gallic acid at a single platform. In addition nanotechnology-mediated approaches are also discussed to enhance bioavailability and therapeutic efficacy.

Objective: The surging cancer incidence has necessitated the synthesis, characterization and production of green synthesized silver nanoparticles and its effective use. The present study was carried out to assess the antineoplastic potential of the green synthesized silver nanoparticles against breast cancer cell lines. Methods: The rapid biological synthesis of silver nanoparticles was done using Withania somnifera, Aegle marmelos and Taraxacum officinale. The synthesized nanoparticles were characterized using Scanning Electron Microscope (SEM), Energy Dispersive X-Ray Spectroscopy (EDX) and Fourier Transform Infra-Red (FTIR) analysis. Further, the antineoplastic potential of the green synthesized nanoparticles were assessed by MTT assay at an ascending concentration of 25, 50, 100, 250, 500μg/ml against MCF-7 (Breast) cancer cell lines. Results: The synthesized nanoparticles were characterized using SEM, EDX and FTIR analysis which confirmed the formation of silver nanoparticles and were of irregular shape with a size of 26 nm, 18 nm, 94 nm, and its IC50 value was 251.2563±0.59µg/ml, 215.5172±0.41µg/ml and 205.7613±0.37µg/ml for Aegle marmelos, Taraxacum officinale and Withania somnifera respectively against MCF-7 cells. Conclusion: The investigation unveils the fact that phytofabricated AgNPs could be exploited as an effective antineoplastic agent for further medical and pharmaceutical applications.

Tinospora is highly distributed in the tropical and subtropical region of India. This climbing deciduous shrub widely reported in China, Bangladesh and Srilanka. The plant is rich in many phytoconstituents that are useful in drug designing. It is highly used against cancer, tumour suppression, and act as an anti-allergic compound. It is commonly known as gudhuchi, belongs to the family Menispermeaceae. Tinospora is most valuable herb known for its medicinal properties from Vedic periods and cures various diseases such as malaria, asthma and urinary disorders. The genus Tinospora consists of many classes of chemicals such as alkaloids, diterpenoids lactones, steroids, aliphatic compounds and polysaccharides. It is the best remedy for both children as well as adults against respiratory tract diseases. The plant shows various antioxidant, anti-hyperglycemic, anti-neoplastic and hepatoprotective properties. In this review article medicinal property, chemical constituents and full description have been explored.

Innovative and specific double dual wavelength, dual ratio subtraction spectrophotometric methods were carried out along with a successive ratio subtraction spectrophotometric method for determination of dacarbazine and its related impurities including toxic and hazardous ones. For determination of dacarbazine by the double dual wavelength method, the absorbance differences between 323 and 350 nm of the zero order absorption spectra of dacarbazine were used. The values of absorbance difference between 267.2 and 286.2 nm of the zero order spectra of 5-amino-imidazole-4 carboxamide were used for its determination by the dual ratio subtraction method. The zero order absorption spectrum of 2-azahypoxanthine at 235 nm was used for its determination after applying the successive ratio subtraction method. ICH guidelines were followed for validation of the developed methods, where linear relationships were obtained in the range of 4–20, 1–16, and 2–20 μg mL−1 for dacarbazine, 5-amino imidazole-4-carboxamide and 2-azahypoxanthine, respectively. Accurate, precise, and specific results were obtained upon applying the proposed methods according to ICH guidelines. Furthermore, the developed methods were successfully applied for determination of dacarbazine in its pharmaceutical formulation. Comparing the results of the developed methods with those of the official USP spectrophotometric method statistically showed no significant difference. The developed methods don't need any sophisticated techniques so they are considered cost effective methods. Moreover, the introduced methods have the advantages of being green where water was used as a solvent. The methods proved to be more economic, fast and simple than other reported HPLC methods.

Trabectedin, an alkylating agent, is used as palliative chemotherapy of soft-tissue sarcoma after failure of first-line treatment. It is labeled as a low cardiac risk profile. We present a case of a lady with metastatic synovial sarcoma with a pre-treatment normal echocardiography, who received 3 cycles of Trabectedin, and presented in cardiogenic shock which reversed back to normal function with vasopressor, diuresis and inotrope support. Case report: A 66-year-old female with metastatic synovial sarcoma of lungs (post right upper lobectomy and chemotherapy), with positive mediastinal and hilar nodes improvement, was transferred in with hypotension and respiratory distress. She was recently started on trabectedin as palliative chemotherapy, about 2 months prior to this admission, received 3 cycles, the last cycle was 4 days prior to admission. There was an elevation of high-sensitivity troponin (peaked to 2000) which trended down. With metastatic disease and ongoing thrombocytopenia (post-chemotherapy), cardiac catheterization was not deemed appropriate, managed medically with inotrope, and pressor support for cardiogenic shock. A nuclear stress test done after weaning off all intravenous medicine showed an LVEF of 55% without any area of ischemic defect. As no other precipitants were identified and with reversibility of cardiac function over time, we considered these events were related to trabectedin toxicity. Discussion: For the use of Trabectedin, there is no specific caution for patients with cardiac disease or risk factors hence labeled as low cardiac risk profile by comprehensive analysis. This case highlights a rare but life-threatening side effect of this drug. It is important to balance the potential of an increase in progression-free survival with chemotherapy versus a life-threatening adverse effect which may counter-effect the mortality benefit and highlights a need for close serial monitoring.

Introduction Venous thromboembolism is a common complication among cancer patients with an estimated risk of 20%. American Society of Clinical Oncology guidelines recommend direct oral anticoagulants for long-term anticoagulation but caution the use of direct oral anticoagulants because of drug–drug interactions with antineoplastic therapies. The clinical impact of these drug–drug interactions is yet to be studied in clinical trials. This study aims to evaluate the effect of the drug–drug interactions on venous thromboembolism recurrence and bleeding. Methods This is a retrospective cohort study that included cancer patients with venous thromboembolism receiving apixaban or rivaroxaban with antineoplastic therapy. The impact of the drug–drug interaction was determined by its effect on the rates of venous thromboembolism recurrence and bleeding in patients with a drug–drug interaction compared to patients with no drug–drug interaction. Results The primary composite endpoint of venous thromboembolism recurrence and bleeding events occurred in 65% versus 62% of patients in drug–drug interaction and non-drug–drug interaction groups accordingly. There was a higher rate of venous thromboembolism recurrence and minor bleeding events with anti-mitotic microtubule inhibitors and a higher rate of minor bleeding events with hormonal therapy and alkylating agents. Among the drug–drug interaction group, there were no major bleeding events reported with mild drug–drug interactions when compared to moderate-to-severe drug–drug interactions. There was no difference in time to venous thromboembolism recurrence between rivaroxaban and apixaban. Conclusion Due to small sample size, our study results could not confirm a higher risk of bleeding or venous thromboembolism recurrence with the drug–drug interactions. Further prospective study is warranted, but clinicians should be aware of these drug–drug interactions and identify them using available literature.

Background There is no clear consensus on the administration of anti-neoplastic agents to patients on peritoneal dialysis. Dose adjustments to prevent serious adverse events are still not established. Thus, the aim of this study was to systematically review current evidence on the use of systemic oncology therapies in peritoneal dialysis. Methods A systematic review was conducted using PubMed, Scopus, and Cochrane. All relevant data was collected, including clinical and pharmacokinetic parameters, with comparison to subjects with normal renal function. Results Sixteen studies were included. All were case reports. Eighteen types of anti-cancer drugs were reviewed. Multiple adverse events and altered pharmacokinetics were reported. Conclusion Data concerning the use of anti-neoplastic drugs in patients on peritoneal dialysis are still sparse. The elimination of anti-cancer agents seems often altered in such patients, resulting in serious adverse events. Based on the available evidence, we suggest the need for dose adjustment of each drug.

A flowering plant of variegated ingredients and psychoactive qualities, Cannabis has long been used for medicinal and recreational purposes. Regulatory approvals have been gained across a broad range of palliative and therapeutic indications, and in some cases, included in standard treatment guidelines.The use of Cannabis and cannabinoid-based-medicines in oncology is summarized in this article. Cannabinoids are classified according to natural and synthetic subtypes and their mechanisms of action expounded. The variability of available products is discussed in the clinical context and data regarding chemotherapy-induced nausea and vomiting, cancer-related pain, anorexia, insomnia, and anxiety are presented. Moreover, immunological and antineoplastic effects in preclinical and clinical trials are addressed. Concepts such as synergism or opposition with conventional treatment modalities, the sequence of administration and dosage, molecular cross-talk and malignancy-cannabinoid congruence, are explored. Finally, side-effects, limitations in trial design and legislation barriers are related.Sufficient evidence supports the use of Cannabis for palliative indications in oncology; however, patients should be carefully selected, guided and followed. Promising research suggests the potent antineoplastic activity, but more data must be accrued before conclusions can be drawn.

The article is all about the anti – cancer drugs approved by the FDA for treating different forms of cancers. Article gives complete idea about each drug which was approved by FDA, which includes the use, route of administration, the dosing & the side effects. The article also gives brief about the pharmacokinetics & pharmacodynamics of the drugs.

In classical Ayurvedic literature, the root preparation of plant Chitrak (Plumbago-zeylanica) is well documented to be having anti-cancer properties. Away from its use as anti-neoplastic drug, it is also a very common ingredient in so many Ayurvedic formulations which are used as herbal digestive and carminative. Many times they can be prescribed to a pregnant woman also, so the present study is designed to assess the teratogenic effect in mice embryos induced by Chitrak as Ayurvedic medicine. After evaluation of 24 fetuses who have received Chitrakroot powder during their anti-natal life period, it can be said that Chitrak is relatively safe for them; however, only a few fetuses have shown subcutaneous hemorrhages in their necks.

Cancers have been the leading cause of death worldwide and poor diet and physical inactivity are major risk factors in cancer-related deaths. Micronutrients such as vitamins and minerals appear to have preventive properties against cancer. One important mechanism by which dietary changes can exert preventive effects on cancer is via the modulation of micronutrient concentrations in target tissues. Many of these micronutrients are available in the form of dietary supplements, and the intake of these supplements is prevalent in various parts of the world. However, in most cases, it is not known which micronutrient (or combination of micronutrients) is best when it comes to lowering the risk of cancer. The present review illustrates the effect of vitamin D and ascorbic acid intake on preventing cancer.

Ginseng, an oriental gift to the world of healthcare and preventive medicine, is among the top ten medicinal herbs globally. The constitutive triterpene saponins, ginsenosides, or panaxosides are attributed to ginseng's miraculous efficacy towards anti-aging, rejuvenating, and immune-potentiating benefits. The major ginsenosides such as Rb1, Rb2, Rc, Rd., Re, and Rg1, formed after extensive glycosylations of the aglycone "dammaranediol," dominate the chemical profile of this genus in vivo and in vitro. Elicitations have successfully led to appreciable enhancements in the production of these major ginsenosides. However, current research on ginseng biotechnology has been focusing on the enrichment or production of the minor ginsenosides (the less glycosylated precursors of the major ginsenosides) in ginseng preparations, which are either absent or are produced in very low amounts in nature or via cell cultures. The minor ginsenosides under current scientific scrutiny include diol ginsenosides such as Rg3, Rh2, compound K, and triol ginsenosides Rg2 and Rh1, which are being touted as the next "anti-neoplastic pharmacophores," with better bioavailability and potency as compared to the major ginsenosides. This review aims at describing the strategies for ginsenoside production with special attention towards production of the minor ginsenosides from the major ginsenosides via microbial biotransformation, elicitations, and from heterologous expression systems.

Introduction: Costs of prophylaxis of chemotherapy-induced (febrile) neutropenia (CIN/FN) have been reduced in recent years by the approval of several biosimilar filgrastim and pegfilgrastim agents. The savings from conversion to biosimilars can be reallocated to provide expanded access to CIN/FN prophylaxis or anti-neoplastic treatment. To illustrate this, we simulated in a panel of 20,000 non-Hodgkin lymphoma (NHL) patients: 1) the savings that could be realized from CIN/FN prophylaxis with biosimilar pegfilgrastim-cbqv over reference pegfilgrastim with or without on-body injector (PEG/PEG-OBI), 2) a model of expanded access to CIN/FN prophylaxis with biosimilar pegfilgrastim-cbqv from cost-savings achieved from conversion from PEG/PEG-OBI, and 3) a model of expanded access to chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab (R-CHOP) for NHL from cost-savings achieved from conversion from PEG/PEG-OBI. Methods: Simulation modeling for a panel of 20,000 NHL patients was conducted from the US payer perspective. Medication costs for PEG/PEG-OBI, pegfilgrastim-cbqv, and R-CHOP drugs were calculated in three ways 1) Q1 2020 average selling price (ASP) derived from CMS Q3 2020 reimbursement limits, 2) Wholesale Acquisition Cost (WAC) from Redbook, and 3) a blended ASP/WAC rate proportionate to the NHL age distribution per Surveillance, Epidemiology, and End Results Program data. These three cost estimate bases were applied to one through six cycles of prophylaxis with conversion rates from PEG/PEG-OBI to biosimilar pegfilgrastim-cbqv ranging from 10% to 100%. The number-needed-to-convert (NNC) to biosimilar pegfilgrastim-cbqv from PEG/PEG-OBI to purchase one additional treatment of pegfilgrastim-cbqv or one additional cycle of R-CHOP chemotherapy was also estimated. Results: Using ASP, cost-savings of biosimilar pegfilgrastim-cbqv over PEG/PEG-OBI in a panel of 20,000 NHL patients ranged from $371,444 (for 1 cycle of prophylaxis at 10% conversion) to $22,286,640 (6 cycles at 100% conversion). The corresponding savings ranged from $4,112,120 to $246,727,200 when using WAC; and from $1,976,194 to $118,571,640 when using the age-proportionate blended ASP/WAC rate. Focusing on the blended ASP/WAC rate, the savings in a single cycle of chemotherapy translated into expanded access to biosimilar pegfilgrastim-cbqv ranging from 524 cycles at 10% conversion from PEG/PEG-OBI to 5,243 cycles at 100% conversion. The savings over six cycles of biosimilar prophylaxis could provide between 3,146 (at 10% conversion) and 31,457 (at 100% conversion) additional cycles of biosimilar pegfilgrastim-cbqv. The NNC from one cycle of PEG/PEG-OBI to biosimilar pegfilgrastim-cbqv to purchase one additional cycle of biosimilar pegfilgrastim-cbqv is 4. In a single cycle of chemotherapy, savings using the blended ASP/WAC rate translated into expanded access to R-CHOP ranging from 282 cycles at 10% to 2,817 cycles at 100% conversion. The savings over six cycles of biosimilar prophylaxis could provide between 1,690 (at 10% conversion) and 16,900 cycles (at 100% conversion) additional cycles of R-CHOP. The NNC from one cycle of PEG/PEG-OBI to biosimilar pegfilgrastim-cbqv to purchase one additional cycle of R-CHOP is 8. Conclusions: These simulation models demonstrate that significant cost savings for supportive cancer care can be generated through conversion to biosimilar pegfilgrastim-cbqv for CIN/FN prophylaxis. The savings generated from conversion from PEG/PEG-OBI can be reallocated on a budget-neural basis to provide expanded access to additional patients/cycles of CIN/FN prophylaxis with biosimilar pegfilgrastim-cbqv or to curative anti-neoplastic treatment. Such efficiency and expanded access enhance the value of cancer care to payers and patients. Disclosures McBride: MorphoSys: Consultancy; Sandoz: Consultancy; Pfizer: Consultancy; Merck: Speakers Bureau; Coherus BioSciences: Consultancy, Speakers Bureau; Bristol-Myers Squibb: Consultancy. MacDonald:Sandoz: Consultancy; MorphoSys: Consultancy; Celgene: Consultancy; Terumo: Consultancy; Rockwell Medical: Consultancy; Janssen: Consultancy; Novartis: Consultancy; Mylan: Consultancy; Coherus BioSciences: Research Funding. Abraham:MorphoSys: Consultancy; Sandoz: Consultancy; Mylan: Consultancy; Janssen: Consultancy; Rockwell Medical: Consultancy; Terumo: Consultancy; Celgene: Consultancy; Coherus BioSciences: Research Funding, Speakers Bureau.

Background: Cancer has been a serious health threat for human especially in developing countries. As the tumor patients are largely in elderly population, the ongoing trend of population aging and increased long-term cancer survivors will add complexity to tumor patients management. However, the tumor patients, aged and with multiple therapeutics, are largely under-served in medication service in China. The aim of this study was to evaluated the effectiveness of an independent anti-neoplastic medication therapy management system for tumor patients management.Methods: An independent, anti-neoplastic medication therapy management (MTM) system, in Shanghai Jiao Tong University affiliated sixth People's Hospital, was established in 2018 as a result of collaboration of onco-chemotherapy, clinical pharmacy and software engineers. The system consists of an independent clinic of pharmacy and MTM software. The software consisted of six modules to enable clinical pharmacists to serve the patients. The six modules are medication therapy review, intervention plan, personal medication record, medication-related action plan, intervention and/or referral, and documentation and follow-up.Results: In a year, 173 tumor patients visited the pharmacy clinic and the averaged clinic visiting count was 2.4 for the all tumor patients. Two thirds patients (117/173) were with one or more identified drug-related problems (DRPs) in medication therapy review. Three leading DRPs are adverse drug reaction, potential drug-drug interaction and non-adherence. Seventy percent of DRPs could be resolved (cure or improved) in four weeks; the medication adherence reached 84%-100% following three or four round of review and intervention.Conclusions: The involvement of clinical pharmacists in polypharmacy tumor patients management increased the communication with oncologists, and could ultimately enhance the effectiveness, safety and rational use of medication.

In this protocol, we outline the procedure for generation of tumor spheroids within 384-well hanging droplets to allow for high-throughput screening of anti-cancer therapeutics in a physiologically representative microenvironment. We outline the formation of patient derived cancer stem cell spheroids, as well as, the manipulation of these spheroids for thorough analysis following drug treatment. Specifically, we describe collection of spheroid morphology, proliferation, viability, drug toxicity, cell phenotype and cell localization data. This protocol focuses heavily on analysis techniques that are easily implemented using the 384-well hanging drop platform, making it ideal for high throughput drug screening. While we emphasize the importance of this model in ovarian cancer studies and cancer stem cell research, the 384-well platform is amenable to research of other cancer types and disease models, extending the utility of the platform to many fields. By improving the speed of personalized drug screening and the quality of screening results through easily implemented physiologically representative 3D cultures, this platform is predicted to aid in the development of new therapeutics and patient-specific treatment strategies, and thus have wide-reaching clinical impact.

Background Several decontamination methods are currently available to reduce the occupational exposure of hospital facilities to conventional anti-neoplastic drugs. Alcohol-based microbicides are not sufficiently efficient in removing chemical contamination and data are lacking on many marketed biocides. Recent data confirm that using a specific chemical decontamination solution is helpful in removing traces of contaminants. Purpose To perform a literature review in order to help pharmacists in choosing a chemical decontamination solution to implement in their compounding unit. Material and methods Articles were searched on Pubmed using the following requests: ‘antineoplastic agents AND cleaning’ or ‘antineoplastic agents AND chemical degradation’ or ‘antineoplastic agents AND chemical decontamination’. Criteria used to classify the performance and usability of decontamination solutions were: decontamination efficiency, number and nature of tested contaminants, hazardousness of the decontamination solution, implementation difficulties and respect of the aseptic environment. Results Two-hundred and seventy-four articles were retrieved following the request application. Two-hundred and fifty-seven articles were discarded for different reasons leading to the analysis of 17 articles. Fifty-nine methods were tested as degradation (n=19) or desorption methods (n=40) with various decontamination efficiencies ranging from ≤10% to 100%. Applying the selection criteria, three decontamination solutions were chosen: sodium hypochlorite, admixture of 10-2 M sodium dodecyl sulfate (SDS) and 70% isopropanol (80/20), marketed two steps towelettes kit (1. Quaternary ammonium solution, 2. Isopropanol). Their inertness to facilities’ surfaces is different and sodium hypochlorite solutions oxide metals. Solutions involving tension-active agents such as SDS may form a film on the facilities surface, which may alter the sterility environment. Conclusion The applied selection criteria led to select only three decontamination solutions. Their application modalities are also to be discussed regarding the biological and chemical facilities’ monitoring. As the solutions were assessed with various methodologies, further studies are necessary to compare them in the same conditions. Because each solution has been tested with different contaminants, new studies are required to confirm their ability to decontaminate other conventional anti-neoplastic drugs. References and/or acknowledgements Vasseur, et al. EJHP 2017;24(Suppl 1):A218. doi:10.1136/ejhpharm-2017–000640.485 Vasseur, et al. PLos One 2018. No conflict of interest.

Background The most common side effects of chemotherapy or radiotherapy are linked to systemic toxicity and toxicity towards rapidly growing cells. In the latter category, oral mucosites, which are quite disabling for patients, occur in 15%–40% of patients treated with conventional chemotherapy, in 70%–90% in those treated with TCSE and in 80% of those who receive radiotherapy for neck or head cancers. Because of pain and difficulty in eating due to mucositis, 16%–32% of these patients require recurrent hospitalisation. Obviously, this side effect bears heavily on the budget of the Italian healthcare system. Purpose To deal with these challenges, hospital pharmacists working with other health professionals have developed new formulations. Material and methods After researching the latest information on Galenic formulations in large literature databases,1 the hospital pharmacists evaluated currently available products and proposed new formulations. Once they prepared the formulations, they developed leaflets for each formulation to be given to the patient and caregiver. Treatments were provided for mucosites assigned a score from 0 to 3 on the WHO scale. Results Of the formulations proposed, the hospital pharmacists adopted six solutions and one gel. Up to August 2017, the only one they produced was a formulation of lidocain and metilprednisolone. Subsequently, they added formulations of Ialuronate-Aloe (30% of the formulations provided) and Misoprostole-artificial saliva (11%), followed by Benzydamine and Supersatura (a solution containing sulphates and chlorides). In July 2018, Doxepin and Bicarbonate formulations were prepared, while the use of lidocain and metilprednisolone continued (36%). Conclusion The new formulations were introduced to maintain and increase oral hygiene, limit the risk of infections, moisturise the oral cavity and relieve pain, all things that were not achievable with the previous formulations. References and/or acknowledgements 1. https://www.mascc.org/assets/Guidelines-Tools/mascc%20isoo%20mucositis%20guidelines%20paper%206jun2014.pdf 2. http://www.salute.gov.it/portale/documentazione/p6_2_2_1.jsp?lingua=italiano&id=2139 3. http://www.cancernurse.eu/documents/EOCCGuidelinesv7.pdf 4. http://www.ukomic.co.uk/pdf/UK_OM_Guidelines.pdf 5. European Oncology Nursing Society(EONS), Oral Mucositis Guidelines, 2005. 6. http://www.palliativecareguidelines.scot.nhs.uk/media/42558/20170119-mouth-care.pdf 7. https://www.esmo.org/Guidelines/Supportive-and-Palliative-Care/Management-of-Oral-and-Gastrointestinal-Mucosal-Injury 8. International Journal of Pharmaceutical Compounding (IJPC). No conflict of interest.

Throughout the world, there are increasing demands for alternate approaches to advanced cancer therapeutics. Numerous potentially chemotherapeutic compounds are developed every year for clinical trial and some of them are considered as potential drug candidates. Nanotechnology-based approaches have accelerated the discovery process, but the key challenge still remains to develop therapeutically viable and physiologically safe materials suitable for cancer therapy. Here, we report a high turnover, on/off-switchable functionally popping reactive oxygen species (ROS) generator using a smart mesoporous titanium dioxide popcorn (TiO2 Pops) nanoarchitecture. The resulting TiO2 Pops, unlike TiO2 nanoparticles (TiO2 NPs), are exceptionally biocompatible with normal cells. Under identical conditions, TiO2 Pops show very high photocatalytic activity compared to TiO2 NPs. Upon on/off-switchable photo activation, the TiO2 Pops can trigger the generation of high-turnover flash ROS and can deliver their potential anticancer effect by enhancing the intracellular ROS level until it crosses the threshold to open the ‘death gate’, thus reducing the survival of cancer cells by at least six times in comparison with TiO2 NPs without affecting the normal cells.

INTRODUCTION Prostate cancer (PCa) is the most common cancer in the North-American man. It was responsible for about 192,000 new cases and 33,000 deaths in the USA in 2020. Surgical resection and systemic androgen deprivation therapy are standard approaches to treat both localized and metastatic PCa (mPCa). The five-year survival from prostate cancer (PCa) without bone metastasis is 56% versus 3% with metastasis There is no cure for the metastatic prostate cancer (mPCa) which often spreads to the hip, spine, and pelvis bones. Therefore, new approaches and combination therapy need to be developed to improve patients's survival. Disulfiram's anti-cancer activity was previously explored and its metabolite ditiocarb-copper complex (CuET) was found to have high anti-cancer activity. The mechanism of action of CuET involves NPL4 aggregation and activation of ER stress, leading to preferential apoptosis of cancer cells. Since altered protein degradation is targeted by CuET, it might display high efficacy in highly mutated PCa. Consequently, we want to propose CuET for the treatment of mPCa. METHODS Survival curve and colony-formation assays in murine dKO cell line harboring PTEN and Rb driver mutations as well as in the human metastatic PC3 cell line, were performed. Anti-metastatic effect of CuET in vitro was assessed through Boyden chamber. In vivo efficacy of systemic treatment with CuET, was studied in dKO model of C57BL/6 mice. RESULTS Our results demonstrate that CuET displays cytotoxicity in dKO and PC3 cells at very low concentrations with respective IC50 of 46.2nM and 90.5nM. In vitro, CuET significantly reduced both the clonogenicity and migration ability of cells. In vivo, systemic treatment with CuET significantly reduced growth of dKO tumor and prevented recurrence of tumors. CONCLUSION Given these positive pre-clinical results, CuET should be investigated for its antineoplastic activity in clinical setting as an adjuvant therapy for mPCa. Citation Format: Daciana Catalina Dumut, Juan B. DeSanctis, Martin Mistrik, Zdenek Skrott, Petr Dzubak, Jiri Bartek, Marian Hajduch, Danuta Radzioch. Dithiocarb-copper complex, CuET, demonstrates anti-neoplastic activity in mouse model of prostate cancer and prevents recurrence of tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1251.

10535 Background: Homologous recombination is a major mechanism of defective DNA repair, but it remains uncertain whether homologous repair deficient (HRD) tumors have favorable prognosis or are more/less likely to respond to treatment than tumors lacking such mutations. Objective: To determine whether lung (NSCLC) and colorectal (CRC) HRD+ tumors have better survival or response to chemotherapy than HRD- tumors. Methods: Patients with de novo stage IV NSCLC or CRC who had next generation sequencing (NGS) between 2015-2018 from one of four cancer centers were identified. Records were curated using the PRISSMM framework to ascertain treatment, overall survival (OS) and progression free survival based on imaging (PFS-I) and oncologists’ notes (PFS-M). Each NSCLC or CRC tumor was categorized as HRD+ if NGS revealed an oncogenic/likely oncogenic mutation in: ATM, BAP1, BARD1, BLM, BRCA1, BRCA2, BRIP1, CHEK2, FAM175A, FANCA, FANCC, NBN, PALB2, RAD50, RAD51, RAD51C, RTEL1, or MRE11A based on the OncoKB database. The tumor was categorized as HRD- if no oncogenic mutation in any of these genes was evident and HRD indeterminate (HRD?) if no mutation was identified but the panel did not include all genes. OS, PFS-I and PFS-M from start of first line therapy were reported by HRD status. The percentage with a good response to first line therapy (≥2x the median) and exceptional response (≥3x the median) was estimated for each endpoint. Results: For NSCLC 4% were HRD+, 59% HRD- and 37% HRD?. For CRC there were 5% HRD+, 60% HRD- and 35% HRD?. There were no significant differences for any survival endpoint between patients who were HRD+ vs HRD- in univariable analyses. The proportion of good and exceptional responders to first line systemic chemotherapy also did not vary by HRD status, though patients with HRD+ CRC were potentially more likely to be exceptional responders. Similarly, no differences between HRD+ and HRD- tumors were apparent for the subgroup receiving platinum containing therapy. Conclusions: NSCLC and CRC patients with somatic mutations in HRD oncogenic genes did not differ from patients lacking such a mutation with respect to OS or PFS. CRC patients with HRD+ tumors may be more likely to be exceptional responders, but sample sizes are limited. By May, the analysis will include breast and pancreatic cancer cases.[Table: see text]

// Rogerio B. Craveiro 1, * , Michael Ehrhardt 1, * , Julia Velz 1 , Martin Olschewski 1 , Barbara Goetz 1 , Torsten Pietsch 2 and Dagmar Dilloo 1 1 Department of Pediatric Hematology and Oncology, Center for Pediatrics, University of Bonn Medical Center, D-53113 Bonn, Germany 2 Department of Neuropathology, University of Bonn, D-53105 Bonn, Germany * These authors have contributed equally to this work Correspondence to: Rogerio B. Craveiro, email: Rogerio.craveiro@ukb.uni-bonn.de Keywords: medulloblastoma, Vandetanib, GDC-0941, targeted therapy, multi-kinase inhibitor (MKI) Received: July 27, 2016 Accepted: December 26, 2016 Published: January 31, 2017 ABSTRACT Medulloblastoma is comprised of at least four molecular subgroups with distinct clinical outcome (WHO classification 2016). SHH-TP53-mutated as well as MYC-amplified Non-WNT/Non-SHH medulloblastoma show the worst prognosis. Here we present evidence that single application of the multi-kinase inhibitor Vandetanib displays anti-neoplastic efficacy against cell lines derived from high-risk SHH-TP53-mutated and MYC-amplified Non-WNT/Non-SHH medulloblastoma. The narrow target spectrum of Vandetanib along with a favourable toxicity profile renders this drug ideal for multimodal treatment approaches. In this context our investigation documents that Vandetanib in combination with the clinically available PI3K inhibitor GDC-0941 leads to enhanced cytotoxicity against MYC-amplified and SHH-TP53-mutated medulloblastoma. In line with these findings we show for MYC-amplified medulloblastoma a profound reduction in activity of the oncogenes STAT3 and AKT. Furthermore, we document that Vandetanib and the standard chemotherapeutic Etoposide display additive anti-neoplastic efficacy in the investigated medulloblastoma cell lines that could be further enhanced by PI3K inhibition. Of note, the combination of Vandetanib, GDC-0941 and Etoposide results in MYC-amplified and SHH-TP53-mutated cell lines in complete loss of cell viability. Our findings therefore provide a rational to further evaluate Vandetanib in combination with PI3K inhibitors as well as standard chemotherapeutics in vivo for the treatment of most aggressive medulloblastoma variants.

Cediranib, a pan-tyrosine kinase inhibitor is showing promising results for the treatment of several solid tumours. In breast cancer, its effects remain unclear, and there are no predictive biomarkers. Several studies have examined the expression profiles of microRNAs (miRNAs) in response to different chemotherapy treatments and found that the expression patterns may be associated with the treatment response. Therefore, our aim was to evaluate the cellular behaviour and differential expression profiles of miRNAs in breast cancer cell lines exposed to cediranib. The biological effect of this drug was measured by viability, migration, invasion and cell death in in vitro assays. Signaling pathways were assessed using a human phospho-receptor tyrosine kinase array. Furthermore, using a miRNA array and quantitative real-time PCR (qRT-PCR), we assessed the relative expression of miRNAs following cediranib treatment. The breast cancer cell lines exhibited a distinct cytotoxic response to cediranib treatment. Cediranib exposure resulted in a decrease in the cell migration and invasion of all the breast cancer cell lines. Treatment with cediranib appeared to be able to modulate the activation of several RTKs that are targets of cediranib such as EGFR and a new potential target ROR2. Furthermore, this drug was able to modulate the expression profile of different microRNAs such as miR-494, miR-923, miR-449a, miR-449b and miR-886-3 in breast cancer cell lines. These miRNAs are reported to regulate genes involved in important molecular processes, according to bioinformatics prediction tools., We would like to thank Olga Martinho and Celine Pinheiro for assisting in the cellular experiments. This study received financial support from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP Proc. no. 2010/16796-0, São Paulo, brazil).

One of the defining characteristics of the malignant phenotype is the ability to evade the host immune system. Immunotherapy as a treatment modality represents a new dawn in the way we think about the treatment of a variety of malignancies. The story of immunotherapy traces its roots to its relationship with malignant melanoma. In this article, we review the intertwined history of immunotherapy and melanoma, including the early significant history, a discussion on immune mechanisms, resistance, local and systemic immunotherapeutic modalities, and speculate on possible novel future treatment options.

Introduction: Approvals of biosimilar pegfilgrastim products in recent years have reduced the costs of single-dose prophylaxis of chemotherapy-induced (febrile) neutropenia (CIN/FN). While reference pegfilgrastim with on-body injector (PEG-OBI) offers convenience to patients over use of next day pre-filled syringe (PFS), PEG-OBI has a reported failure rate of 1.7-6.9% that predisposes patients to increased risk of CIN/FN episodes. Incremental FN-related hospitalizations (FN-HOSP) associated with PEG-OBI failure contribute to the cost differential between PEG-OBI and assured prophylaxis with biosimilar PEG-PFS. Cost savings generated from conversion to biosimilar PEG-jmdb create opportunities for providing expanded access on a budget-neutral basis to additional CIN/FN prophylaxis or anti-neoplastic treatment. Hence, in a panel of 15,000 patients with diffuse large B-cell lymphoma (DLBCL), we aimed to: 1) quantify the cost-savings from assured prophylaxis with biosimilar PEG-jmdb over PEG-OBI accounting for device failures, 2) simulate the additional CIN/FN prophylaxis that could be achieved from the cost-savings, and 3) model the expanded access to anti-neoplastic treatment with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) that could be provided on a budget-neutral basis through reallocation of cost-savings. Methods: Simulation analysis in a panel of 15,000 DLBCL patients at risk for CIN/FN from the US payer perspective utilized. Costs of medication were based on Q1 2020 average selling price (ASP) for PEG-OBI, PEG-jmdb, and R-CHOP drugs derived from CMS Q3 2020 reimbursement limits; cost of PEG-OBI and PEG-jmdb administration per CMS Outpatient Prospective Payment System; between one and six cycles of prophylaxis; conversion rates from PEG-OBI to biosimilar PEG-jmdb ranging from 10% to 100%; and PEG-OBI failure rates of 1% to 7%. Differential base rate of FN-HOSP in NHL (rate of FN-HOSP without colony-stimulating factor [CSF] minus rate with CSF) was 10.03% over a 6-cycle regimen with 56% occurring in cycle 1 (Chrischilles et al., Cancer Control 2002; 13.25% with CSF, 23.28% without). FN-HOSP costs in 2012 of $25,676 per episode for NHL patients (Tai, J Oncol Pract 2017) were adjusted per the Consumer Price Index for Medical Care to $31,914 for 2020. Results: Conversion from PEG-OBI to biosimilar PEG-jmdb in a panel of 15,000 DLBCL patients generated savings ranging from $379,230 (for one cycle of prophylaxis at 10% conversion) to $22,753,800 (6 cycles at 100%) considering the cost of medication plus administration. These cost-savings could provide access to between 110 (1 cycle at 10% conversion) and 6,623 (6 cycles at 100%) additional cycles of PEG-jmdb on a budget-neutral basis, or between 58 and 3,452 cycles of R-CHOP, respectively. Taking incremental FN-HOSP costs due to PEG-OBI failure into consideration, cost-savings in cycle one from conversion to PEG-jmdb, ranged from $406,118 (at 10% conversion and PEG-OBI failure of 1%) to $5,674,454 (at 100% conversion and 7% PEG-OBI failure). These savings translated into expanded access to between 118 additional cycles of PEG-jmdb or 62 cycles of R-CHOP (at 10% conversion and 1% PEG-OBI failure) and 1,652 cycles of PEG-jmdb or 861 cycles of R-CHOP (at 100% conversion and 7% PEG-OBI failure). Over a 6-cycle regimen, savings increase to $2,323,394 (at 10% conversion and 1% PEG-OBI failure) to $26,114,789 (at 100% conversion and 7% PEG-OBI failure). These additional savings increased expanded access to PEG-jmdb to between 676 additional cycles of PEG-jmdb or 353 cycles of R-CHOP (at 10% conversion and 1% PEG-OBI failure) and 7,601 cycles of PEG-jmdb or 3,962 cycles of R-CHOP (at 100% conversion and 7% PEG-OBI failure). Conclusions: CIN/FN prophylaxis with biosimilar PEG-jmdb generates substantial cost savings compared to PEG-OBI when considering drug and administration costs. Savings further increase when the costs of FN-HOSP related to PEG-OBI failure are taken into account. Reallocation of savings realized through conversion to biosimilar pegfilgrastim-jmdb provide expanded access to additional CIN/FN prophylaxis and anti-neoplastic treatment on a budget-neutral basis while reducing risk and associated hospitalization costs associated with inadequate prophylaxis due to device failure. Disclosures McBride: Coherus BioSciences: Consultancy, Speakers Bureau; Merck: Speakers Bureau; Pfizer: Consultancy; Sandoz: Consultancy; MorphoSys: Consultancy; Bristol-Myers Squibb: Consultancy. MacDonald:Sandoz: Consultancy; Coherus BioSciences: Research Funding; Mylan: Consultancy; Novartis: Consultancy; Janssen: Consultancy; Rockwell Medical: Consultancy; Terumo: Consultancy; Celgene: Consultancy; MorphoSys: Consultancy. Abraham:Sandoz: Consultancy; Mylan: Consultancy; Janssen: Consultancy; Rockwell Medical: Consultancy; Terumo: Consultancy; Celgene: Consultancy; Coherus BioSciences: Research Funding, Speakers Bureau; MorphoSys: Consultancy.

Introduction Oxaliplatin is a third generation anti-neoplastic platinum compound (organo-platinum complex) used in the treatment of several solid tumours either as a single agent or in combination with other chemotherapy drugs. Hypersensitivity reactions to oxaliplatin are uncommon, with most reports indicating an incidence of 1–5%. The severity of reactions may vary from grade 1 side effect in line of skin flushing and/or rashes to very severe, life-threatening systemic anaphylaxis (grade 3/4). Following mild to moderate hypersensitivity reactions, steroids and/or antihistamines could be administered, after which the patient can be re-exposed to the drug. In severe hypersensitivity reactions however, oxaliplatin must be discontinued while alternative chemotherapeutic regimen or even other forms of therapy should be considered. Case report A 56 year old woman with colorectal cancer who was commenced on adjuvant oxaliplatin therapy developed Hypersensitivity reaction about 2 hours of the first oxaliplatin administration, for which the drug was discontinued and the symptoms improved. She had similar reactions in 2 subsequent attempts at administering same drug, after which the drug was changed. A placebo infusion was administered twice with no untoward reactions. Management and outcome: With each reaction, the drug was immediately discontinued and she was promptly given intranasal oxygen and corticosteroids. She was premedicated with anti-histamines and corticosteroids prior to subsequent cycles. Oxaliplatin was consequently discontinued and she experienced no further hypersensitivity reaction to the subsequent drug regimen. Discussion Hypersensitivity reactions to oxaliplatin, though a rare occurrence, are more likely idiosyncratic; with more cases being reported in recent times.

Introduction: Colorectal cancer (CRC) is the third leading cause of cancer related deaths in the United States. It was responsible for about 51,000 deaths during 2019. Surgical resection and systemic chemotherapy are standard approaches to treat both localized and metastatic CRC (mCRC). However, the effect of the chemotherapy depends on the characteristics of the individual tumor, for instance CRC subtypes with a microsatellite instability (MSI) tend to have better prognosis and response to both chemotherapy and immune check-point inhibition. Recently, Disulfiram's anti-cancer activity was explored and its metabolite ditiocarb-copper complex (CuET) was found to have high anti-cancer activity. The mechanism of action of CuET was proposed to act through p97 segregase adaptor NPL4 and activation of endoplasmic reticulum stress leading to preferential apoptosis of cancer cells. Since altered protein degradation pathway is targeted by CuET, this compound might display high efficacy in highly mutated colorectal cancers. Methods: To assess CuET anti-cancer activity in vitro, we performed survival curve assays and colony-formation assays in both murine hypermutated colorectal cancer cell line MC-38 as well as in human KRAS mutant and MSI HCT116 cell line. We also evaluated anti-metastatic effect of CuET on both cell lines through migration-invasion assays in Boyden chamber setting. We assessed in vivo efficacy of systemic treatment with CuET alone or in combination with irinotecan, against MC-38 model in immunocompetent C57BL/6 mice. We characterized tumor growth, mice survival and tumor histopathology. Results: Our results demonstrate that CuET displays cytotoxicity in MC-38 and HCT116 cells at very low doses with respective IC50 of 46nM and 88nM. CuET also significantly reduces the ability of both cell lines to grow and form colonies under sustained treatment. Additionally, CuET is effective in significantly reducing cancer cell migration and invasion through porous membrane in vitro. Furthermore, systemic treatment with CuET significantly reduced tumor growth in mice and prolonged survival when compared to controls. Conclusion: CuET demonstrates cytotoxic activity against hypermutated colorectal cancer cells both in vitro and in vivo and should be further investigated in clinical trials. Citation Format: Daciana Catalina Dumut, Juan B. De Sanctis, Martin Mistrik, Zdenek Skrott, Petr Dzubak, Jiri Bartek, Marian Hajduch, Danuta Radzioch. Disulfiram anticancer metabolite, dithiocarb-copper complex, demonstrates anti-neoplastic activity against hypermutated colorectal cancers [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5246.

Autophagy is an evolutionarily conserved self-cannibalization process commonly found in all eukaryotic cells. Through autophagy, long-lived or damaged organelles, superfluous proteins, and pathogens are sequestered and encapsulated into the double-membrane autophagosomes prior to fusion with lysosomes for ultimate degradation and recycling. Given that autophagy is deemed both protective and detrimental in malignancies, the clinical therapeutic utilization of autophagy modulators in cancer has attracted immense attentions over the past decades. Dependence of tumor cells on autophagy during amino acid insufficiency or deprivation has prompted us to explore the underlying autophagy regulatory mechanisms to inject amino acid degrading enzymes and enzyme-based strategies into therapeutic maneuvers of autophagy in cancer.

VAL-083 (Dianhydrogalactitol) is a bi-functional DNA targeting agent that is currently being evaluated in a phase II trial in recurrent glioblastoma (GBM) patients. The goal of the present study was to further elucidate the anti-neoplastic effects and signaling pathways through which VAL-083 functions. We examined the efficacy of VAL-083 against a panel of eight GBM stem cells (GSCs) isolated from newly diagnosed GBM patients. The panel of GSCs were molecularly phenotyped based on the expression of several proteins including EGFR, EGFRvIII, and MGMT as well as several stem cell markers including SOX2, NESTIN, MST1, CD133, TFRC, and OLIG2. The effect of VAL-083 on GSC growth was measured using WST-1 reagent and the effect on GSC’s ability to form neurospheres was assessed by microscopy. Our results show that VAL-083 inhibits neurosphere formation in all eight GSCs. Further, VAL-083 inhibits the growth of GSCs with an IC(50) of 200–2000 nM. To identify the molecular pathways affected by VAL-083, control and VAL-083-treated GSCs were subjected to proteomic analysis using reverse phase protein array (RPPA) technology. The RPPA examined the expression of a total of 297 proteins and phosphoproteins. It was found that VAL-083 affects the expression of several proteins and phosphoproteins central to GBM growth. A key protein significantly downregulated by VAL-083 was bromodomain protein 4 (BRD4). This is a salient important finding because BRD4 has been implicated in several cancers including GBM, and agents that target BRD4 are undergoing development as anti-neoplastic agents. In summary, we report that VAL-083 is effective in halting the growth of a panel of GSC isolated from newly diagnosed GBM patients and the underlying mechanism involves downregulation of BRD4.

Single crystal X-ray studies of regioselectively synthesized fluoro-substituted dispiro-oxindole 9 revealed that the structure belongs to the monoclinic space group P21/n with four molecules in the unit cell. The structure was also investigated by AM1, PM3, and DFT studies. Compound 9 exhibits high potency against the HeLa cell line.

Gypsogenin ( L 1 ; 3 - hydroxy - 23 - oxoolean - 12 - en - 28 - oic acid ), a natural saponin, was isolated from the boiling water extract of Gypsophila arrostii roots. In addition, the derivatives gypsogenin thiosemicarbazone ( L 2 ; 23 - [(aminocarbonothioyl)hydrazono] - 3 - hydroxolean - 12 - en - 28 - oic acid ) and gypsogenin thiosemicarbazone glyoxime ( L 3 H 2 ; (3β) - 3 - hydroxy - 23 - [({[(1Z,2E) - N - hydroxy - 2 - (hydroxyimino)ethanimidoyl]amino}carbonothioyl)hydrazono] olean - 12 - en - 28 - oic acid ) as well as the Cu(II) and Co(II) complexes of L 3 H 2 were prepared. The structures were established on NMR analysis ( 1 H, 13 C NMR, HMBC, HMQC, and NOESY), FT-IR and completed by analysis of LC/MS. Furthermore, the antiproliferative effects of the Co(II) and Cu(II) complexes of the gypsogenin derivatives were assayed in human promyelocytic leukemia (HL 60) cells. These complexes were found to be potent anticancer agents with concentrations that inhibited 50% of proliferation (I p C 50 ) between 5 μM and 40 μM. Cell death was distinguished by HO/PI double staining. The Co(II) complex of L 3 H 2 has shown approximately %50 apoptotic effect at 10 μM concentration. Paclitaxel has been used as positive control.