Impact of age and medical comorbidity on adjuvant treatment outcomes for stage III colon cancer: a pooled analysis of individual patient data from four randomized, controlled trials.

BACKGROUND: Adjuvant oxaliplatin plus capecitabine or leucovorin/5-fluorouracil (LV/5-FU) (XELOX/FOLFOX) is the standard of care for stage III colon cancer (CC); however, there is disagreement regarding oxaliplatin benefit in patients aged >70. In most analyses, the impact of medical comorbidity (MC) has not been assessed. Efficacy and safety of adjuvant XELOX/FOLFOX versus LV/5-FU were compared with respect to age and MC using pooled data from four randomized, controlled trials, selected for access to patient-level MC data and including commonly endorsed and utilized regimens. PATIENTS AND METHODS: Individual data from patients with stage III CC in NSABP C-08, XELOXA, X-ACT, and AVANT were pooled, excluding bevacizumab-treated patients. Patients were grouped by treatment, MC (low versus high), or age (<70 versus ≥70), and compared for disease-free survival (DFS), overall survival (OS), and adverse events (AEs). Multivariable Cox proportional hazards regression controlled for gender, T stage, and N stage. RESULTS: DFS benefits were shown for XELOX/FOLFOX versus LV/5-FU regardless of age or MC, although benefits were modestly attenuated for patients aged ≥70. Hazard ratios were 0.68 (P < 0.0001) and 0.77 (P < 0.014) for <70 and ≥70 age groups; 0.69 (P < 0.0001) and 0.59 (P < 0.0001) for Charlson Comorbidity Index ≤1 and >1 groups; and 0.70 (P < 0.0001) and 0.58 (P < 0.0001) for National Cancer Institute Combined Index ≤1 and >1 groups. OS was also significantly improved in all groups. Grade 3/4 serious AE rates were comparable across cohorts and MC scores and higher in patients aged ≥70. Oxaliplatin-relevant grade 3/4 AEs, including neuropathy, were comparable across ages and MC scores. CONCLUSIONS: Results further support consideration of XELOX or FOLFOX as standard treatment options for the adjuvant management of stage III CC in all age groups and in patients with comorbidities, consistent with those who were eligible for these clinical trials.

Phase II study of eribulin mesylate (E7389) in patients with metastatic castration-resistant prostate cancer stratified by prior taxane therapy.

BACKGROUND: Treatment options remain limited for patients with castration-resistant prostate cancer (CRPC). We evaluated eribulin mesylate (E7389), a nontaxane halichondrin B analog microtubule inhibitor, in patients with metastatic CRPC with or without previous taxane exposure. PATIENTS AND METHODS: Men with histologically proven CRPC, with or without prior taxane exposure, were enrolled in an open-label, single-arm phase II trial. Patients received eribulin mesylate 1.4 mg/m(2) as a 2- to 5-min i.v. bolus infusion on days 1 and 8 of a 21-day cycle. The primary efficacy end point was prostate-specific antigen (PSA) response rate. RESULTS: In total, 108 patients were assessable for safety (50 were taxane-pretreated) and 105 for efficacy in the per-protocol population. The median age of patients was 71 years and median number of cycles was 4. PSA decreases of ≥ 50% were achieved in 22.4% and 8.5% of taxane-naive and taxane-pretreated patients, respectively. The most common grade 3/4 adverse event was neutropenia, seen in 22.4% of chemo-naive and 40% of taxane-pretreated men. Grade 3 peripheral neuropathy occurred in none of the taxane-naive patients and 6.0% of taxane-pretreated patients. CONCLUSION: Eribulin mesylate demonstrated activity and a relatively favorable toxicity profile in metastatic CRPC.

Hyperalimentation of the cancer patient with protein-calorie undernutrition.

Because protein-calorie undernutrition is common in patients with neoplastic disease, nutritional support is often recommended. It is uncertain, however, that methods of supplemental alimentation successful in noncancerous subjects are suitable in cancer patients. We measured elemental balances, serum proteins, anthropometrics (triceps skinfold and mid-arm muscle area), and creatinine/height ratio in 15 undernourished patients with advanced cancer and in 10 noncancer undernourished controls during central venous or enteral hyperalimentation and found the following. (a) During central venous hyperalimentation, cancer patients showed significantly less improvement than the noncancerous controls in body weight (median increment, 5 kg in cancer patients and 8.5 kg in noncancerous), albumin (0.1 g/dl in cancer patients and 0.5 g/dl in noncancerous patients), creatinine/height ratio (4% of standard in cancer and 10% of standard in noncancer), and mid-arm muscle area (4% of standard in cancer and 11% of standard in noncancer). During enteral hyperalimentation, gains in body weight and albumin by cancer patients were significantly inferior to those in noncancerous subjects. Triceps skinfold increments, in contrast, were similar during both central venous and enteral hyperalimentation for cancer and noncancerous patients. (b) While nitrogen retention was similar in cancer and noncancer patients, the cancer group retained significantly less magnesium and phosphorus (delta Mg in cancer patients, 3.2 mEq/day central, -2.7 mEq/day enteral; delta Mg in noncancer patients, 11.9 mEq/day central, 10.1 mEq/day enteral; delta P in cancer patients, 0.13 g/day central, 0.07 g/day enteral; delta P in noncancer patients, 0.27 g/day central, 0.33 g/day enteral). The poorer balances of cancer patients were caused by increased urinary, not fecal, loss. These findings indicate a partial block in repletion of lean body mass or abnormal composition of newly deposited lean body mass when undernourished patients with advanced cancer receive hyperalimentation.