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

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.