The aim of this pilot study was to assess the safety of the angiogenesis inhibitor thalidomide(Drug information on thalidomide) (Thalomid) given in combination with standard chemotherapy to patients with advanced nonsmall-cell lung cancer. Patients with unresectable stage IIIA, IIIB, or IV disease were enrolled starting in July 1999. Patients received standard chemotherapy with paclitaxel (Taxol) at 225 mg/m² over 3 hours and carboplatin(Drug information on carboplatin) (Paraplatin) at an area under the concentration-time curve of 6 (AUC in mg/mL · min), with thalidomide at a starting daily dose of 200 mg.
Stage IIIA and IIIB patients without pleural effusion received two cycles of chemotherapy followed by radiotherapy plus thalidomide. Stage IIIB patients with pleural effusion and stage IV patients received six cycles of chemotherapy plus thalidomide. The thalidomide dose was escalated (if tolerated) by 200 mg/wk to a target dose of 1,000 mg/d, and could continue for up to 6 months. To date, nine patients have been enrolled: one with stage IIIA disease, two with stage IIIB disease, and six with stage IV disease. We are now able to present early safety and efficacy data.
The most frequent side effects noted were fatigue, myalgia, constipation, and neuropathy. One patient experienced both grade 3 fatigue and grade 3 myalgia with the first cycle, but was able to tolerate subsequent dose titrations well. One patient had grade 3 nausea. All patients experienced grade 1 constipation while on thalidomide. Seven out of nine patients experienced grade 1 neuropathy. Two patients with previous chemotherapy experienced grade 4 neutropenia lasting more than a week and one patient had grade 4 thrombocytopenia. These hematologic toxicities were thought to be most likely due to the chemotherapy, and not the thalidomide.
The mean tolerated thalidomide dose was 711 mg (range: 2001,000 mg). The range of months on thalidomide was 1 to 5 with all but one patient continuing on study. No responses have been seen. All six patients completing two cycles of treatment had stable disease (one with stage IIIB with pleural effusion, one with stage IIIB without pleural effusion, and four with stage IV disease). Two patients have completed four cycles of therapy and remain with stable disease (both with stage IV disease). One patient who had stage IIIB disease with pleural effusion progressed after three cycles of treatment and has been taken off study. Additional follow-up data will be available at the time of presentation.
CONCLUSION: Thalidomide is safe and well tolerated in combination with standard chemotherapy in the treatment of advanced nonsmall-cell lung cancer.