Radiotherapy with Concomitant Continuous Cisplatin Infusion for Unresectable Tumors of the Upper Aerodigestive Tract

Abstract

A phase I-II study was initiated in February 1991 of concomitant radiation and cisplatin (CDDP) in the treatment of unresectable head and neck squamous cell carcinomas (n = 12). The first patient was treated palliatively for a cervical recurrence of laryngeal cancer. The 11 other patients had locally advanced (stage IV) previously untreated carcinomas of the oropharynx (n = 9), hypopharynx (n = 1), or cervical node with unknown primary site (n = 1). Standard external radiation was carried out up to a total dose of 60 Gy/6 weeks (7 MeV electron beam) for the first patient and 72 Gy/8 weeks (Co60 beam) for the other 11 patients. CDDP was infused continuously during the entire radiation treatment, 5 days/week. The starting dose was 4 mg/m2/day and was escalated by increments of 1 mg/m2/day; dose-limiting toxicity was observed at 7 mg/m2/day. Neutropenia (grade 4, one patient; grade 3, three patients) and thrombocytopenia (grade 3, one patient; grade 2, one patient) were the limiting factors. Therefore, the recommended dose of CDDP is 6 mg/m2/day. All patients but one completed the scheduled radiation. For the entire group, mucositis was not more severe than that observed with radiotherapy alone. There was no nephro-, oto-, or neurotoxicity. A complete response was obtained in eight (66%) patients. Of these, four were free of disease 12-34 months after completion of treatment and one had a total glossectomy for a tongue necrosis. For the whole series, the mean overall survival was 16 months posttreatment. Pharmacokinetic analysis indicated the total cisplatin accumulation at the end of treatment to be 743-1551 ng/ml. Accumulation of ultrafilterable platin was noted in only one patient (137 ng/ml at the end of treatment).

Concurrent Cisplatin-Based Radiotherapy and Chemotherapy for Locally Advanced Cervical Cancer

“…16,18,[32][33][34][35][36][37][38][39][40] Two trials reported improvements in local control of tumors and survival in pa-*A grade of 0 indicates the absence of an adverse effect, a grade of 1 a minimal effect, a grade of 2 a mild effect, a grade of 3 a moderate effect, and a grade of 4 a severe effect. Eight patients who did not receive radiotherapy were excluded from the analysis.…”

Cisplatin and Radiotherapy in the Treatment of Locally Advanced Head and Neck Cancer

“…Renal and haematologic toxicities, and also stomatitis, were the most frequently reported doselimiting factors. In a number of trials, a daily cisplatin dose of 6 mg/m 2 was considered to be the upper limit if the higher-grade toxicities were to be avoided (3,5,37). Even though cisplatin is more toxic than many other anticancer drugs, it has the advantage that its toxicity does not overlap with the radiation-produced side effects.…”

“…Daily low-dose cisplatin has been better tolerated in several studies (3,5,37,38). Choi et al (4) have also used the daily low-dose cisplatin schedule, and planned interruptions during the treatment to prevent excessive toxicity.…”

The role of amifostine in the treatment of head and neck cancer with cisplatin-radiotherapy

“…Daily low‐dose cisplatin has been better tolerated in several studies (Bachaud et al. 1997; Jeremic et al.…”