Fractionated carboplatin radiosensitization - A phase I dose-escalation study

Carboplatin is one of the most common drugs used for radiochemotherapy of c ancer. However, the best way to combine the drug with fractionated radiothe rapy has not been established. In the present study the authors investigate d which maximum tolerated daily bolus dose of carboplatin would allow safe radiopotentiation for 10 consecutive radiotherapy days, the scheme being re peated twice during the 6 weeks that a conventional radiotherapy scheme las ts. Seventy-two patients with lung or pelvis malignancies were included in a dose escalation study. Twenty-four patients comprised the first baseline cohort and were treated with radiotherapy alone. The daily dose of carbopla tin was escalated starting from 38 mg/m(2) daily (for 10 days) and increasi ng by 7 mg/m(2) per day. Six patients were to be included in each cohort. A ll 12 patients treated at the 38 mg/m(2) and 45 mg/m(2) dose level complete d two cycles of 10-day carboplatin treatment with no grade III-IV toxicity. Granulocyte colony-stimulating factor effectively averted the incidence of neutropenia and allowed the administration of the second carboplatin 10-da y cycle in five of six patients at the 52 mg/m(2) daily dose level. Platele t grade III-IV toxicity was observed in all 12 patients (six supported with granulocyte colony-stimulating factor and six with granulocyte colony-stim ulating factor and recombinant human erythropoietin) treated at the 59 mg/m (2) daily dose level and none of them received the second cycle of chemothe rapy. Twelve patients were treated at the same dose level using amifostine 500 mg before carboplatin infusion. Two patients interrupted chemotherapy b ecause of severe nausea and vomiting. Nine of 10 who accomplished the 10-da y treatment had platelet levels more than 90,000/mu l on day 28 and complet ed the second 10-day cycle without severe toxicity. Acute radiation toxicit y did not increase in the carboplatin cohorts. In this study the authors es tablished a high-dose fractionated carboplatin schedule that can be safely administered during radical radiotherapy.