Feasibility study on daily administration of cis-diamminedichloroplatinum(II) in combination with radiotherapy

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 0.6-2.1×10⁹/l) after 3-5 weeks of treatment, while seven developed severe thrombocytopenia (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 1.8-2.1×10⁹/l) was observed in three patients requiring postoponement of treatment in one of them. Despite the lack of i.v. hydration no renal toxicity developed. In the total group of 21 patients, 7 (5 in the 8-mg group, 2 in the 6-mg group) developed severe mucositis (head and neck 5, esophagus 1, bronchus 1). Significant skin reactions (small patchy areas of epidermolysis) were seen in two patients. Although renal function was not impaired in either of the treatment groups, with or without hydration, a drop in serum electrolytes occurred in several of the patients. These results suggest that the combined use of radiotherapy and daily doses of cis-platinum is feasible. Although the dose of 8 mg/m² per day appears to be toxic, it seems possible to use 6 mg/m² per day. Further studies on the possible role of cis-platinum as a radiosensitizer are warranted and will require careful studies of the effects on normal tissues and tumours.