Phase I clinical trial of chemoimmunotherapy in combination with radiotherapy in stage IIIB cervical cancer patients

Abstract

To determine the feasibility and toxicity of a chemoimmunotherapy regimen in combination with radiotherapy in stage IIIB cervical cancer patients, cisplatin 10-20 mg/m2 intravenous (iv) weekly, 5-fluorouracil (5FU) 500 mg/m2 (24-h infusion) weekly, interferon α-2a 3 MU subcutaneously 3 days a week, and 13-cis-retinoic acid 0.5 mg/kg/day orally were given in concurrence with 8-week period of radiotherapy and continued for another 4 weeks after finishing radiotherapy. The dose of cisplatin was escalated from 10 mg/m2 in the first group of three patients (level 1) to 15 mg/m2 in the second group of three patients (level 2) and to 20 mg/m2 in the third group of two patients (level 3) if the former groups could tolerate the drugs well. Patients in levels 1 and 2 had tolerable toxicities. Two patients in level 3 experienced grade 4 leukopenia, so chemoimmunotherapy was discontinued after 2 and 3 cycles orderly. After recovery from toxicities, they continued with radiotherapy. In conclusion, cisplatin 15 mg/m2, 5-FU 500 mg/m2 weekly, interferon α-2a 3 MU subcutaneously 3 days a week, and 13-cis-retinoic acid 0.5 mg/kg/day orally in combination with radiotherapy in stage IIIB cervical cancer patients is tolerable. Leukopenia is the dose-limiting toxicity.

Efficacy and Safety of Immunotherapy for Cervical Cancer—A Systematic Review of Clinical Trials

“…Various nonspecific immune system modulators, including interferon α, interleukin 12, extract derived from agaricus blazei murill kyowa, mycobacterium tuberculosis (Z-100) or streptococcal preparations (OK-432) as well as sizofiran and thymopentin or cornyebacterium parvum have been studied for cervical cancer [ 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 ]. All agents affect the immune system in a general way at different levels.…”