Search

This phase II clinical trial evaluated the antitumour response of Kahalalide F (KF) 650 microg/m(2) given as a 1-h weekly infusion in advanced malignant melanoma patients, both untreated and those who relapsed or progressed after one line of systemic therapy. Of 24 enrolled patients (median age, 55 years; range, 28-89), 14 patients had been previously treated with chemotherapy or biological therapy. No RECIST responses occurred; five chemotherapy-naïve patients with cutaneous melanoma had disease stabilisation for > or = 3 months; median progression-free survival was 1.7 months (95% CI, 1.2-1.9 months); and median overall survival was 10.8 months (95% CI, 5.0-upper limit not reached). The most common laboratory toxicities were non-cumulative increase of transaminases (ALT/AST) and gamma-glutamyltransferase (GGT). No patients experienced leukopenia and thrombocytopenia during the study. KF was a well-tolerated and safe chemotherapy regimen. Despite a favourable safety profile, this trial was closed after the first stage because of the lack of objective response in patients with malignant melanoma.

Background: Li-Fraumeni syndrome is a dominantly inherited disorder characterized by early-onset breast cancer, soft-tissue sarcomas and osteosarcomas, acute leukemia, adrenocortical neoplasms and central nervous system tumors. Germline mutations in gene TP53 are identified in a percentage of affected families., Patients and Method: Eight families with aggregation of childhood sarcomas, brain tumors, breast cancers in pre-menopausal women, and renal tumors were screened for TP53 germ-line mutations. SSCP and posterior direct sequencing were performed for genetic analysis. We also report a previously undescribed family with the Li-Fraumeni syndrome carrying a germline mutation., Results: Seven families fulfilled so-called Li-Fraumeni like criteria and one fulfilled classical criteria. A new germ-line mutation in codon 238 at exon 7 of the gene TP53 was identified in the family fulfilling classical criteria. This mutation has not been previously reported., Conclusions: The clinical heterogeneity as well as the molecular complexity and consequences of mutation analysis and genetic counseling make it necessary to develop protocols in this area. A multidisciplinary approach is needed; this approach should be coordinated by a Familial Cancer Genetic Counseling Unit.

The incidence and risk factors for fungal infection were assessed in 291 patients who had solid tumors and were undergoing autologous peripheral blood stem cell transplantation. The first 162 patients received prophylactic itraconazole, and 129 patients received nystatin. Empiric amphotericin B was given at day 7 of febrile neutropenia. Fungal infections developed in 52 patients: 47 (16%) were superficial and 6 (2%) were systemic. Itraconazole prophylaxis and only a few days of febrile neutropenia were independently associated with a decrease in the incidence of superficial infections. Only two patients required empiric amphotericin B. Systemic antifungal prophylaxis does not seem to be justified for patients with solid tumors and autologous peripheral blood stem cell transplantation. Empiric amphotericin B may be safely started at day 7 of febrile neutropenia.

HER-2/neu and p53 expression, conventional clinical and pathologic prognostic factors, were evaluated in a retrospective series of 283 node-positive breast cancer patients. Overexpression was determined by immunohistochemistry in formalin-fixed paraffin-embedded tissue blocks. Twenty one percent were HER-2/neu positive and 40% p53 positive. HER-2/neu expression was related to axillary lymph node metastasis (P=0.014), inflammatory infiltrates (P=0.004), and the absence of oestrogen (ER) (P=0.0026) and progesterone (P=0.01) receptors (PR). p53 expression was related to lymph node involvement (P=0.03), necrosis (P=0.036), absence of ER (P=0.028) and PR (P=0.065). p53 was not associated with outcome. HER-2/neu was an unfavourable prognostic factor for disease-free (DFS) (P=0.05) and overall survival (OS) (P=0.02) in univariate analysis. Multivariate analysis showed that the number of involved axillary nodes (P<0.00001), age (P=0.004), grade (P=0.04), and PR (P=0.04) were independent predictors for OS. ER-positive patients treated with adjuvant tamoxifen had shorter DFS and OS when they were HER-2/neu positive.

In the randomised clinical trial E1684, the administration of interferon (IFN) alpha-2b resulted in prolonged disease-free and overall survival in high-risk melanoma patients following surgical resection. However, and considering the cost and toxicity of IFN, the convenience of its widespread use should be evaluated. The aim of this study was to analyse the cost-effectiveness ratio of adjuvant therapy with IFN alpha-2b in melanoma patients versus an untreated control group. A Markov model was used to compare two hypothetical cohorts of 1000 patients aged 50 years, according to the clinical outcome of the E1684 study. The cohort of patients treated with IFN alpha-2b has an increased overall survival of 1.90 years during the patient's lifetime. The incremental discounted cost per life year gained of IFN versus observation is 9015 Euros according to the projection generated by the model. The sensitivity analysis demonstrated that changes in the most relevant study end-points do not modify the study outcome. In conclusion, in high-risk melanoma patients following surgical resection, the cost-effectiveness of IFN alpha-2b (at a dose of 20 MU/m2/day, 5 days per week for one month, followed by 10 MU/m2 TIW, up to one complete year of therapy) versus an untreated control group is within the limits established in health economics to determine if adoption of a new treatment is economically justified and is comparable with other interventions in which cost-effectiveness is acceptable to the National Health System.

Objective: To review the different salvage chemotherapy regimens according to the prognostic factors based on the response to the different therapeutic alternatives., Methods: The conventional rescue chemotherapy regimens, as well as the role of surgery, new drugs and therapeutic modalities, particularly high dose second and third line chemotherapy, were reviewed., Results/conclusions: Germ cell testicular tumor is the paradigm of curable tumors of the adult. Whereas the cure rate for stage I tumors is higher than 98%, patients with advanced stage tumors have a lower cure rate. Approximately 10% of the patients with good-prognosis factors and 30%-50% of those with poor-prognosis factors show tumor progression or recurrence after first line chemotherapy using cisplatin-based combinations. Patients who have recurrence after first line chemotherapy have a 40% probability of achieving second complete remission with second line chemotherapy, but will be sustained in only 20% of the patients, although rare cases of advanced pure seminoma that recurred have shown a cure rate of 55% with second line chemotherapy. New strategies have been developed using new drugs such as taxanes or high doses of well-known chemotherapeutic agents with autologous hematopoietic rescue that have been utilized with success in patients with refractory germ cell testicular tumors. A global analysis of the patients treated with third line chemotherapy shows a sustained complete remission rate of 22%. However, this percentage can only be increased to up to 50% for patients with no adverse factors.

The aim of this work was to assess whether cancer patients presenting high anxiety levels or poor adaptation to cancer experience higher levels of postchemotherapy nausea, regardless of the emetogenicity of the chemotherapy schedule. Sixty-three patients were interviewed before receiving their chemotherapy schedule and some psychological variables were assessed. Nausea intensity was also assessed after treatment. The results showed that patients with relatively higher levels of nausea reported higher levels of anxiety prior to chemotherapy and lower levels of adaptation to cancer. Thus, evidence for a modulating effect of psychological factors in postchemotherapy emesis is suggested.

Hereditary nonpolyposis colorectal cancer (HNPCC) diagnosis is based either on the so-called "Amsterdam 1 criteria" or "Amsterdam 2 criteria", which includes extracolonic neoplasms associated with Lynch II syndrome. Many families are suspected of having a hereditary predisposition to cancer and may benefit from close surveillance. We describe a family (family 1) with suspected HNPCC at the beginning who fulfilled the Amsterdam 1 criteria over the course of its follow-up. We also describe an Amsterdam 2 family (family 2) with a very young affected individual. Both of them received genetic counseling and screening recommendations. A total colonoscopy was done to an asymptomatic member of family 1 and he was diagnosed with an early-stage colon cancer. He underwent subtotal colectomy because of the high risk of metachronous lesion. Screening recommendations must be the same in Amsterdam 2 families as in Amsterdam 1. Both families show the importance of considering the family history when hereditary criteria are suspected.

Background: alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG), and lactate dehydrogenase (LDH) closely follow the course of germ cell tumors (GCTs) and are widely used for diagnosis, prognosis, and follow-up purposes. The objective of this study was to assess the concordance of tumor markers at the time of diagnosis and recurrence., Methods: The authors reviewed the records of 794 patients with GCTs treated in three Spanish hospitals from 1977-1996 and analyzed the concordance between AFP, HCG, and LDH levels at diagnosis and first and second recurrence. A positive marker was defined as a level of AFP > 10 ng/mL, HCG > 5 IU/L, or LDH > the upper limit of normal. One hundred twenty-five patients were identified who developed a first recurrence (123 had marker levels recorded). The median age was 27 years (range, 14-78 years). Histology was seminoma in 36 patients (29%) and nonseminomatous GCT (NSGCT) in 87 patients (71%)., Results: Seventy-nine patients (64%) had elevated tumor markers at diagnosis and 76 (62%) at first recurrence. An elevated marker was present at first recurrence in 58 of 79 patients (73%) with initially positive markers and in 18 of 44 patients (41%) with initially negative markers. In 84 of 123 patients (68%), the same marker pattern (positive or negative) was present at the time of diagnosis and at first recurrence, 78% in seminomas and 64% in NSGCTs. The earliest indicator of recurrence was an elevated marker in patients with NSGCTs and a radiologic finding in patients with seminomas. Thirty patients developed a second recurrence, 27 of whom (90%) had the same marker pattern as at first recurrence., Conclusions: Tumor marker pattern at diagnosis is not a good predictor of the pattern at recurrence, particularly in patients with NSGCTs. Marker assessment should be included in the follow-up schedule regardless of levels at the time of diagnosis. Early detection of recurrence should not rely only on marker levels, even in patients with elevated levels at presentation., (Copyright 2000 American Cancer Society.)

To prospectively analyze factors that influence peripheral blood stem cell (PBSC) collection and hematopoietic recovery after high-dose chemotherapy (HDC), 39 patients received cyclophosphamide 4 g/m(2) and rHuG-CSF (Filgrastim) 5 &mgr;g/kg/day. Leukapheresis was started when CD34(+) cells/mL were > 5 x 10(3). A minimum of 2 x 10(6) CD34(+) cells/kg was collected. Median steady-state bone marrow CD34(+) cell percentage was 0.8% (range, 0.1 to 6). Thirty-two patients received HDC with autologous PBSC transplantation plus Filgrastim. A median of 2 (range, 0 to 6) leukapheresis per patient were performed and a median of 6.3 x 10(6) CD34(+) cells/kg (range, 0 to 44.4) collected; four patients failed to mobilize CD34(+) cells. The number of cycles of prior chemotherapy had an inverse correlation with the number CD34(+) cells/kg collected (r = -0.38; p < 0.005). Patients with <7 cycles had a higher predictability for onset of leukapheresis than patients with (3) 7 (93% versus 50%; p < 0.005). The four patients who failed to mobilize had received >/=7 cycles. The number of CD34(+) cells/kg infused after HDC had an inverse correlation with days to recovery to 0.5 x 10(9) neutrophils/L and 20 x 10(9) platelets/L (r = -0.68 and -0.56; p < 0.005). The effect of these factors on mobilization and hematopoietic recovery were confirmed by multivariate analysis. Requirements for supportive measures were significantly lower in patients given a higher dose of CD34(+) cells/kg. Therefore, PBSC collection should be planned early in the course of chemotherapy. Larger number of CD34(+) cells/kg determined a more rapid hematopoietic recovery and a decrease of required supportive measures.

Objective: To analyze the clinical outcome of patients diagnosed with growing teratoma syndrome (GTS) at a single center during a long follow-up., Patients and Methods: Eleven patients with GTS are reported. GTS lesions were located in the metastatic sites involved at disease presentation. Involved sites were: retroperitoneum in 9 patients; lung in 3; supraclavicular lymph nodes in 2, and inguinal lymph nodes in 1. Surgical resection of the masses was the treatment of choice., Results: Twenty-four surgical procedures were performed: 4 thoracotomies; 2 supraclavicular; 1 inguinal, and 17 retroperitoneal node resections. Three patients have not relapsed since surgery of the masses, at 37+, 110+ and 118+ months. Eight patients have relapsed, 6 with mature teratoma and 2 (22%) with cancer. To date, all the patients are alive, 6 of them without disease and 5 with teratoma after resection of the masses., Conclusions: GTS is an infrequent entity. Involved sites are only at locations previously affected by the disease. The treatment of choice is surgical resection but recurrence is common. Efforts should be done to complete resection of the masses.

Malignant pleural mesothelioma soon leads to death no matter what type of treatment is provided. We discuss the clinical signs, prognostic factors and treatment given in 41 cases managed over the past 13 years in our oncology department. 32% had been exposed to asbestos, 61% were 60 years old or younger, 71% had a Karnofsky's index > or = 80% and 63% were stage I (Butchart). The first symptom leading to diagnosis was pain in 66% and mean time between first symptom and diagnosis was 3 months. Thirty patients never experienced full remission of disease: 15 were treated with palliative chemotherapy (CHT), 1 with palliative radiotherapy (RT), 5 with partial pleurectomy (PP) plus RT and/or CHT. Nine were given symptomatic treatment only. Only 11 (27%) patients experienced full remission after treatment: 7 had had extrapleural pneumonectomy, 2 had been given CHT and RT series and 4 had undergone PP with or without RT and/or CHT follow-up. Only 3 of these patients were still alive with no relapse more than 1 year later. Mean survival was 8 months. Univariate analysis revealed that the prognostic factors influencing survival were age and Karnofsky's index. Patients initially treated with surgery had a higher rate of survival. In conclusion, only Karnofsky's index and age were prognostic factors in our series. The better survival of patients initially treated surgically is probably related to prior screening.

Background: Advanced ovarian neoplasm has bad prognosis. There is little knowledge as to the effect of surgical and chemotherapy treatments on long-term survival., Methods: Seventy-two patients with advanced epithelial ovary carcinoma (53 stage III and 19 stage IV) were treated according to a treatment regimen with reduction surgery, five cycles of chemotherapy with cyclophosphamide, adriamycin and cisplatin (CAP) followed by second revision laparotomy., Results: The rate of response for the CAP schedule was 80%, of which 16 patients (23%) showed complete response (CR), 7 (10%) partial microscopic response (PMiR) and 33 (47%) partial macroscopic response (PMR). Complete resection of residual masses was performed on the second laparotomy in 14 of the 33 patients with parital response. The median survival for all the group was 36 months with overall actuarial survival of 27% at 10 years. The survival of the group of patients with CR was significantly longer than that of PMiR and other groups. Significant differences favorable for the group of partial response with second attempt radical surgery were found versus the group in which te second surgical resection was not radical. FIGO III stage and prechemotherapy tumor size less than 5 cm were found to have favorable effect in the rate of response and survival., Conclusions: The use of CAP chemotherapy achieved complete response in 23% of the patients studied. This group of patients showed to have a greater probability of longer survival. Second attempt surgery on the second laparotomy offers therapeutic benefits when radical.

Metastatic sarcomas have a poor prognosis with current therapeutic regimens. High dose chemotherapy (HDC) has proved to be efficient in a selected group of solid tumors. Nine patients with high grade metastatic sarcomas were treated with HDC followed by autologous bone marrow transplantation. Four patients received HDC as a consolidation of the complete response (CR) obtained with chemotherapy (CT) and two of them were free from disease at 27 and 41 months, respectively. Other four patients had a disease total or partially refractory to conventional CT, and in one case the sensitivity to the chemotherapeutical agents was unknown. In these five cases a partial response was observed in two of the three who had measurable response parameters, but all of them died because of disease progression in a short period of time. These results suggest that there are active HDC schedules on metastatic sarcomas, but its possible benefit would be limited to the consolidation of a CR obtained with previous CT. HDC is a therapeutical alternative under investigation in patients with metastatic sarcomas with an indication that could be extended to cover localized sarcomas with poor prognosis.

Background: Non-Hodgkin's lymphomas (NHL) originated in the otorhinolaryngological (ORL) area are rare diseases and its therapy is poorly established., Methods: The diagnostic features, treatment and outcome based on therapy of 34 NHLs originated in the ORL area and seen in the Oncology Service from the Hospital de la Santa Creu i Sant Pau during a ten year period were reviewed., Results: The predominant primary localization was the tonsil (17 patients), followed by rhinopharynx (8), massive involvement of Waldeyer's ring (4), and oropharynx, maxillary sinus and larynx in the remaining cases. In 26 patients the diagnosis was high-grade lymphoma. The stage distribution was 8 patients (24%) in stage I, 16 in stage II (47%), 3 in stage III (9%), and 5 in stage IV (16%). The treatment was heterogeneous and consisted in chemotherapy in 29 patients (38%), radiotherapy in 5 (15%) or the combination of both in 16 (47%). Eleven patients relapsed (38%), more commonly those treated with radiotherapy. The specific actuarial survival was 69%., Conclusions: NHL originated in the ORL area are uncommon neoplastic diseases, with a commonly dramatic response to chemotherapy. This should be the initial therapeutic modality in all cases.

Background: The reduction of iatrogenesis is fundamental in the treatment of germ-cell testicular tumors (GTT) because of the high incidence of cures achieved. On the other hand, the tumoral mass and the serum concentration of the beta fraction of the gonadotropin hormone (CGH) and of alphafetoprotein allow the differentiation of 2 clear prognostic groups; those for which the intensity of chemotherapy may be adapted to reduce its collateral effects and improve the results., Methods: In the Oncology Department of the Hospital de la Santa Creu i Sant Pau 23 patients with GTT of good prognosis were treated between 1984-1990. These patients were given the combination of etoposide-cisplatin (EP) over the same period. Twenty patients with a bad prognosis received the alternative scheme of bleomycin-vincristine-methotrexate-cisplatin/etoposide-cisplatin- phosphamide (BOMP/EPI)., Results: In comparison to the classical treatment with cisplatin-vinblastine-bleomycin (PVB) the EP association demonstrated less iatrogenesis except in regards to the formation of granulocytopenia which was higher. The BOM/EPI combination conditioned greater hematological toxicity during the acute phase and the first observations suggested a diminution of chronic iatrogenesis., Conclusions: These results indicate that chemotherapy in testicular cancer may be adapted to the aggressiveness of the with the aim to thereby reduce global toxicity.

Twenty-five untreated patients with extensive stage small cell lung cancer (ESSCLC) were treated with carboplatin (CBDCA) (500 mg/m2) given as a 24-hour infusion every 21 days. Thirteen patients responded for an overall response rate of 52% (95% confidence limits, 32% to 72%) with 3 complete responses (CR) (12%; 95% confidence limits, 0% to 25%). The median duration of response was 4.5 months. The median survival time was 8 months with three long-term survivors (12%) at 27, 33, and 43 months from the start of CBDCA treatment. Ninety-two courses of CBDCA were administered and one treatment-related death occurred. The main toxicity was myelosuppression. Grade 3 or 4 hematologic toxicity (hemoglobin level, less than 8 g/dl; granulocyte count, less than 1900/microliters; and platelet count, less than 49,000/microliters) was observed as follows: neutropenia in 7 courses (8%) and in 7 patients (28%), decreased hemoglobin level in 13 courses (15%) and in 7 patients (28%), and decreased platelet count in 10 courses (11%) all Grade 3 and in 8 patients (32%). This study demonstrates that at this dose and schedule CBDCA is a highly active drug in ESSCLC and it has tolerable toxicity.

Seventy-two patients with advanced ovarian cancer received CAP chemotherapy followed by laparotomy and 'second-effort' surgery. The overall response to CAP therapy was 80%. A complete pathological response (CPR) was obtained in 16 patients and partial microscopic (PMiR) and macroscopic responses in 7 and 33 cases, respectively. The actuarial survival for the entire group was 36% at 50 months with a median survival of 34 months. No significant differences in survival between the CPR and PMiR groups were found. Radical second-effort surgery showed a somewhat beneficial effect. The tumor size before chemotherapy (less than 5 cm) and FIGO stage III had a significantly favorable effect on response rate and survival.

Thirty-four patients with locally advanced or metastatic esophageal cancer were treated with cisplatin 35 mg/m2/day x 3 days in bolus, plus bleomycin 15 mg/day x 3 days, as an 18 h infusion, every 21-28 days. Twenty-nine are evaluable for response. Objective response was seen in 15 (52%, 95% confidence limits 35-69%) patients. Toxicity was mild. Twelve patients with locoregional disease were treated with this combination followed by radiotherapy and three of them are alive without disease at 18, 22 and 36 months. This combination warrants further study in the setting of combined treatment.

The protocole of multidisciplinary therapy of the tongue and base of the tongue tumors in the "Hospital de la Sta. Creu i Sant Pau" is presented. The exposition of the management trends by surgery, radiotherapy and chemotherapy, in our protocole, is followed by the review of the therapeutic indications with special enphasis in the topographic ones in order to plan the surgical treatment. The non advanced tumors will be as well treated by intersticial radiotherapy as by surgery. In the treatment of the advanced tumors the multidisciplinary managament results essential. Depending on the degree of invasion, the topography of the tumor and the outline of therapeutic trials, the therapy will be chosen.

A combination of hormonal therapy and chemotherapy (diethyl-estilbestrol or orchiectomy plus cyclophosphamide) was administered to 14 patients with histologic proof of untreated stage D prostatic adenocarcinoma with poor prognosis. Objective responses were obtained in 11 out of the 14 patients (78%), two of which were considered as complete regressions (14%). Response duration lasted for a mean of 9.5 months and the survival reached a mean of 14 months. The authors feel that is worth-while to treat very advanced cases of prostatic carcinoma with hormonal therapy and chemotherapy association.