Phase I study of a 3-drug regimen of gemcitabine/cisplatin/pemetrexed in patients with metastatic transitional cell carcinoma of the urothelium.

OBJECTIVES: Gemcitabine (G) plus cisplatin (C) is standard care for metastatic transitional cell carcinoma (TCC) of the urothelium. Pemetrexed (P), alone or in combination with G, is active in metastatic TCC. However, the safety and efficacy of P combined with GC therapy is unknown. This phase I trial was designed to determine the maximum tolerated dose (MTD) of GC followed by P+G in patients with metastatic TCC. METHODS: Cohorts of 3 to 6 patients received escalating doses 28-day cycles (maximum 6 cycles): G 800-1,000 mg/m2 on days 1 and 15; P 400-500 mg/m2 on day 15; and C 50-70 mg/m2 on day 1. All patients received folic acid, vitamin B12, and full supportive care. The 3+3 standard phase I escalation rule was used to determine MTD. RESULTS: Fifteen patients registered: 13/15 white males; median age 70 years (range, 53-82); 11/15 had KPS>or=90. At dose level 0, 2/4 patients experienced unrelated DLTs, and 1 patient was replaced (completed<1 cycle). Dose escalation proceeded to dose level 1. At level 1, 4/6 patients experienced DLTs; dosing decreased to level 0 and 4/5 patients experienced DLTs. The MTD was not determined. The 2 patients that completed 6 cycles both had partial responses. Grades 3-4 hematologic toxicities included neutropenia (60%), leukopenia (20%), and febrile neutropenia (13%). CONCLUSION: Adding P to the standard GC regimen as first-line therapy for metastatic TCC produced no benefit. The MTD exceeded therapeutic gemcitabine and cisplatin doses for urothelial cancer and thus the study was aborted.

Outcomes among African-American/non-African-American patients with advanced non-small-cell lung carcinoma: report from the Cancer and Leukemia Group B.

BACKGROUND: Among patients diagnosed with advanced non-small-cell lung carcinoma (NSCLC), African-Americans have lower survival rates than non-African-Americans. Whether this difference is due to innate characteristics of the disease in the two ethnicities or to disparities in health care is not known. We investigated whether the disparity in survival would persist when patients were treated with similar systemic therapies (i.e., in phase II and phase III Cancer and Leukemia Group B [CALGB] trials). METHODS: We assessed 504 consecutive patients (458 non-African-American and 46 African-American) receiving systemic chemotherapy in CALGB studies for advanced NSCLC during the period from 1989 through 1998. Clinical and demographic characteristics, treatment received, and survival data were obtained from the CALGB database. Cox's proportional hazards model was used to assess the effect of race/ethnicity on survival after adjustment for other known prognostic factors. All statistical tests were two-sided. RESULTS: The unadjusted 1-year survival rate was 22% (95% confidence interval [CI] = 13% to 38%) for African-American patients and 30% (95% CI = 26% to 35%) for non-African-American patients, a statistically significant difference (8%; 95% CI on the difference = 5% to 12%; P =.03). Multivariable adjustment for the effect of treatment arm, histology, and metastatic site at presentation did not alter the worse outcome for African-American patients. However, the effect of race/ethnicity disappeared after adjustment for performance status and weight loss. African-American patients were more likely than non-African-Americans to present with a poor performance status (83% versus 60%) and substantial weight loss (41% versus 27%) and to be unmarried (59% versus 28%), disabled (31% versus 15%), unemployed (17% versus 7%), and Medicaid recipients (30% versus 8%). CONCLUSIONS: The relationship that we observed between poor performance, weight loss, and socioeconomic status suggests that social circumstances lead to African-Americans presenting with poorer prognostic features.