A phase I study of thalidomide, capecitabine and temozolomide (TCT) in advanced cancer

Abstract

13122 Background: The aim is to develop a novel oral immuno-chemotherapy regimen against advanced cancers. Methods: Patients were enrolled in cohorts of 3 or 6 in a standard phase I design. Thalidomide 100 mg was kept stable for all cohorts. If well tolerated after 1 week, capecitabine and temozolomide (TCT) were given daily without rest and escalated one at a time until dose limiting toxicity (DLT) occurred. If no DLT occurred within 28 days (1 cycle), the following group was enrolled into the next dose level. Results: Twenty-three patients with advanced cancers have been treated in this study. All patients have been evaluated for toxicity and response. Eighty cycles of TCT have been administered (1–13 cycles/patient). Patient characteristics: Median age 59 (31–79), PS ECOG 1 (0–2). Type of cancer: renal (7), bladder (2), pancreatic (2), prostate (2), colon (2), and lung, gastric, synovial sarcoma, angiosarcoma, anal, nasopharyngeal, breast, esophageal (1 each). Prior to TCT, all patients had objective documentation of progressive metastatic disease after a median of 2 therapies (range 0–4). Objective response: Four subjects (17%) achieved partial response (renal 1, gastric 1, prostate 2), and 4 patients (17%) had stable disease (renal 1, colon 1, pancreas 2), adding to a clinical benefit of 34%. Toxicity: Treatment was well tolerated. Common toxicities included grade 3 thromboses 17%; and grade 1–2: hand-foot syndrome, fatigue, sensory neuropathy, nausea, vomiting, and neutropenia. Based on DLT within the first 28 days, the MTD of daily TCT therapy was thalidomide 100 mg, capecitabine 2000 mg and temozolomide 100 mg. With long-term treatment, majority of the patients required dose interruptions due to fatigue, hand-foot syndrome, and neutropenia. Dose level 2.5 was implemented: daily thalidomide and 3-weeks-on 1-week-off capecitabine and temozolomide. Six patients were treated at dose level 2.5 without toxicities. Conclusions: TCT is an effective palliative oral chemo-immunotherapy for patients with advanced cancer. The recommended dose for a phase II trial is dose level 2.5, including thalidomide 100 mg daily, capecitabine 2000 mg/day and temozolomide 100 mg/day three-weeks on and one-week off regimen. [Table: see text]