A phase I clinical trial of low-dose interferon-alpha-2A, thalidomide plus gemcitabine and capecitabine for patients with progressive metastatic renal cell carcinoma.
BACKGROUND
We have conducted a phase I trial to determine the maximum tolerated dose of gemcitabine in combination with interferon, thalidomide and capecitabine.


METHODS
Patients received oral capecitabine 1,000 mg/m(2 )per day, divided in 2 daily doses, 2 weeks on, 1 week off; subcutaneous interferon-alpha 1 mIU twice a day without an interruption; daily oral thalidomide 200 mg/day for the first 7 days, then escalated to 400 mg/day without an interruption. Gemcitabine was given by intravenous administration over 30 min on day 1, week 1 and day 8, week 2. Initial dose level of gemcitabine was 400 mg/m(2). The dose of gemcitabine was the phase I variable. One cycle was 3 weeks.


CONCLUSIONS
We treated 12 patients, 6 patients were entered at a dose level of 0 (gemcitabine 400 mg/m(2)) and 6 patients entered at a dose level-1 (gemcitabine 200 mg/m(2)). Eight of 12 patients completed at least 12 weeks of therapy. Three partial responses and two stable disease were observed. The remaining patients had progressive disease. Non-hematologic toxicity was either grade 1 or 2. Hematologic toxicity at dose level 0 consisted of 3 patients with grade 3/4 neutropenia, and 1 patient with grade 3 thrombocytopenia. At dose level-1 grade 1/2 neutropenia was observed.


CONCLUSIONS
The completion of our phase I experience determined our maximum tolerated dose to be dose level-1. The phase II trial is currently being proposed for patients with rapidly growing clear cell, other histologies that may contain sarcomatoid elements or collecting duct tumor.
Amato
Robert J
RJ
The Methodist Hospital Research Institute, Genitourinary Oncology Program, 6560 Fannin Street, Suite 2050, Houston, TX 77030, USA. ramato@tmh.tmc.edu
Khan
Muhammad
M
D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000069287:Capecitabine; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006402:Hematologic Diseases / Q000139:chemically induced / Q000453:epidemiology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D009362:Neoplasm Metastasis; D011994:Recombinant Proteins; D013792:Thalidomide / Q000008:administration & dosage; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D003841:Deoxycytidine; D013792:Thalidomide; D000069287:Capecitabine; D005472:Fluorouracil; D000093542:Gemcitabine