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Feasibility study on daily administration of cis-diamminedichloroplatinum(II) in combination with radiotherapy
Abstract:
In experimental models cis-diamminedichloroplatinum(II) (cis-platinum) showed to have a radioenhancing effect. The feasibility of daily administration of cis-platinum in combination with radiotherapy was studied in 21 patients with locally advanced inoperable cancers (head and neck 7, esophagus 5, bronchus 3 and others 6). The tumours were squamous cell (15), or adenocarcinoma (6). Radiotherapy was delivered in one (180 cGy; 5 patients) or two (each of 125 cGy; 16 patients) fractions per day to a cumulative dose of 3000-6800 cGy, while cis-platinum was administered at a total daily dose of 8 mg/m2 (14 patients) or 6 mg/m2 (7 patients), in one single or two divided injections (total dose 168-352 mg cis-platinum). Fourteen patients received a total daily cis-platinum dose of 8 mg/m2 with 4 l of i.v. hydration. Severe myelosuppression occurred in 10/14 patients (range white blood cell count nadirs 0.6-2.1 X 10(9)/l) after 3-5 weeks of treatment, while seven developed severe thrombocytopenia (less than 75 X 10(9)/l). All patients became anaemic. Due to this myelosuppression, radiation treatment had to be postponed in four patients for 18-35 days. Eight patients developed bronchopneumonia, two of them had a septicaemia and one died. One patient with a bronchial carcinoma developed necrotizing pneumonitis with a cavity outside the tumour area and subsequent severe pulmonary fibrosis within the radiation field. Seven patients received cis-platinum at 6 mg/m2 per day without i.v. hydration. A moderate leukopenia (white blood cell count nadirs 1.8-2.1 X 10(9)/l) was observed in three patients requiring postponement of treatment in one of them.(ABSTRACT TRUNCATED AT 250 WORDS)