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Purpose To assess safety and efficacy of folinic acid, 5-fluorouracil, gemcitabine (FFG) and folinic acid, fluorouracil, oxaliplatin (FOLFOX4) regimens with added bevacizumab as first-line treatment in patients with advanced colorectal cancer (CRC). Patients and Methods Patients with Stage III unresectable or Stage IV adenocarcinoma of the colon or rectum were randomly assigned to either FFG weekly for 6 weeks of an 8-week cycle or FOLFOX4 every 2 weeks. After FDA approval, bevacizumab 5 mg/kg was added every 2 weeks. Treatment continued until disease progression. Planned enrollment was 190 patients. Primary endpoint was overall response rate (ORR); secondary endpoints included evaluation of adverse events, time to progression (TTP), and overall survival (OS). Disease Control Rate (DCR; % of patients with complete or partial responses or stable disease) was a post hoc analysis. Results The trial was stopped prematurely due to low enrollment. Of 84 enrolled patients (42 to each arm), 36 patients (18 in each arm) received bevacizumab. ORR was greater (P = .002) for FOLFOX4 (17/42; 40.5%) than for FFG (4/42; 9.5%); however, TTP, OS, and DCR results were not statistically different comparing FOLFOX4 and FFG. Peripheral neuropathy was more frequent (P =

The exceedingly high rates of distant metastatic recurrence following successful surgical resection of early-stage tumors would suggest that pancreatic adenocarcinoma is a systemic disease at the time of diagnosis in the vast majority of patients, and therefore a compelling case can be made for a neoadjuvant treatment approach in almost all patients. Although the first national trial of neoadjuvant therapy for resectable pancreatic cancer (ACOSOG Z5041) only recently opened, single-institution experiences have supported this form of treatment sequencing for nearly two decades. However, outside of large referral centers with disease-specific investigators committed to clinical and translational research in pancreatic cancer, confusion remains over how to define, on preoperative imaging, what is resectable and what is not (so called locally advanced or borderline resectable pancreatic cancer). In an attempt to clarify the anatomy of resectable, borderline, and locally advanced disease, Varadhachary and colleagues from the University of Texas M. D. Anderson Cancer Center proposed, in this journal in 2006, an objectively defined, computed tomography (CT)-based classification which distinguished borderline resectable from both resectable and locally advanced pancreatic cancer. 1 The Varadhachary definitions considered venous abutment and encasement (without occlusion) to be resectable, in the absence of tumor extension to the celiac or superior mesenteric (SMA) arteries, as this operational definition was developed for the conduct of clinical trials of neoadjuvant treatment sequencing. There was no intent to use this definition outside of such clinical trials, and this definition of ‘‘resectable’’ was not intended to support a surgery-first strategy for patients who may require vascular resection and reconstruction. The Varadhachary definitions also assumed the technical capability to resect and reconstruct the superior mesenteric-portal vein (SMPV) confluence when necessary and that the major determinant of margin status (R status) was the tumor‐artery (celiac, hepatic, SMA) relationship (Table 1). Katz and colleagues in 2008 reported 160 patients with borderline resectable disease (using the Varadhachary definition) treated at M. D. Anderson Cancer Center and introduced three types of borderline resectable disease, now often referred to as Katz type A, B, and C. 2 Type A patients were those with borderline resectable tumor anatomy as defined in the Varadhachary manuscript. Type B patients were borderline resectable because of a concern for possible extrapancreatic metastatic disease and included those with CT findings suspicious for, but not diagnostic of, metastatic disease as well as those with known local‐regional lymph node metastases. It may be reasonable in 2010 to add to this

The purpose of this study was to determine the efficacy and toxicity of amonafide in unresectable or recurrent head and neck cancer and to determine if the degree of toxicity with amonafide correlated with the acetylator phenotype of the patient. Thirty patients were registered on the study and received amonafide, 300 mg/m2, over two hours each day for five consecutive days every 21 days. There was one partial response [39] which lasted four months. The dose limiting toxicity was myelosuppression. Acetylator phenotype was determined prior to treatment using HPLC to quantitate caffeine metabolites in urine samples after administration of caffeine. This pharmacokinetic evaluation was performed in 21 patients and revealed that (17/21) 81% of the patients were slow acetylators and 19% of the patients were rapid acetylators. No association was found between acetylator phenotype and toxicity in our patient population. Based on this study, it appears that amonafide given at 300 mg/m2 for 5 consecutive days every 21 days is not active in squamous cell carcinoma of the head and neck, and that acetylator status does not correlate with toxicity.

Twenty evaluable patients with newly diagnosed brain metastases underwent treatment with a novel dose/schedule of dexamethasone aimed at reducing steroid toxicity during palliative radiation therapy. All patients received twice daily dexamethasone starting at 8 mg bid for four days then 4 mg bid for four days then 2 mg bid until the last day of radiation therapy. The radiation prescriptions were not standardized varying from 2000 cGy/5 fractions to 5800 cGy/29 fractions. Fourteen patients received dexamethasone for a minimum of 24 hours before their first radiation treatment and 7 (50%) experienced improvement in neurologic symptoms/signs prior to starting radiation treatments. Fourteen patients completed the planned course of radiation and dexamethasone. Only 1 patient needed to restart dexamethasone within 30 days of finishing radiation because of steroid reversible neurologic deficits. Steroid toxicity was mild including hyperglycemia (1), candida esophagitis (1), steroid pseudorheumatism (2), peripheral edema (1) and steroid withdrawal syndrome (1). Only two toxic events were recorded in patients receiving steroids less than 21 days. Twice daily dexamethasone appears to provide good clinical results with minimal morbidity.

Twenty-five patients with refractory, metastatic carcinoma of the breast were treated with continuous ambulatory 5-fluorouracil (5 FU) infusion (200 to 300 mg/m2/day) through a chronic indwelling central venous catheter. All patients had had extensive previous treatment, including hormonal therapy in 20/25 patients (80%), radiation therapy in 18/25 patients (72%), and an average of 4.6 previous chemotherapy drugs per patient (range 1–10). Twenty-three of 25 patients (92%) had had previous bolus 5 FU. Seventeen of 25 patients (68%) had two or more metastatic sites of involvement and 17/25 patients (68%) had visceral involvement. Results: complete remission −1/25 (4%), partial remission −7/25 (28%), stable disease −6/25 (24%), and progressive disease −11/25 (44%), for an overall response rate of 8/25 (32%). Median duration of response was 6 months. Toxicities included hand-foot syndrome, mucositis, diarrhea, and nausea and vomiting, and required treatment interruption and/or dose attenuation in 9/25 patients (36%). No myelosuppression or serious catheter-related problems were seen. We conclude that continuous 5 FU infusion is a potentially effective salvage treatment that may provide meaningful palliation in some patients with carcinoma of the breast, in spite of extensive previous treatment.