title: A Medical Research Council phase II trial of alternating chemotherapy and radiotherapy in small-cell lung cancer. The Medical Research Council Lung Cancer Working Party.
abstract: In a non-randomised study in six centres in the UK, 24 patients with previously untreated small-cell lung cancer of limited extent were treated with a regimen of alternating chemotherapy and radiotherapy to assess response, toxicity, and the feasibility of applying such a regimen on a multicentre basis in the UK. The intention was to give six courses of chemotherapy on five consecutive days at 4-week intervals: etoposide 75 mg m-2 on days 1, 2, and 3; doxorubicin 40 mg m-2 on day 1; cisplatin 100 mg m-2 on day 2; and cyclophosphamide 300 mg m-2 on days 2, 3, 4 and 5. A dose of 20 Gy thoracic radiotherapy was to be given following the 2nd and the 3rd courses, and one of 15 Gy following the 4th course. After 12 patients had been admitted, the cisplatin dosage was reduced to 80 mg m-2 because of unacceptable toxicity. Two patients were withdrawn during treatment on review of their histology because their diagnosis was found to be incorrect. Only one patient of the 12 treated with cisplatin 100 mg m-2 was able to complete treatment, compared with five of the eligible ten given the lower dosage. Among the 22 patients with confirmed small-cell disease, a complete response was reported in 14 (64%) and a partial response in a further three (total response rate 77%). Myelosuppression was the commonest serious adverse effect. It occurred in 19 of the 24 patients and gave rise to septicaemia in five, four of whom were receiving the higher cisplatin dose. Sixteen patients required blood transfusion and ten platelet transfusion. Vomiting, oesophagitis, and peripheral neuropathy occurred in 12, four and four patients, respectively, and radiation pneumonitis developed in two. Treatment was considered a contributory cause of death in four. The working party concluded that the alternating regimen was feasible in only a small proportion of centres in the UK, and decided not to embark on a multicentre randomised trial comparing alternating with conventional scheduling.
authors.affiliation: MRC Clinical Oncology and Radiotherapeutics Unit, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: N M
authors.initials: NM
authors.lastname: Bleehen
authors.forename: D J
authors.initials: DJ
authors.lastname: Girling
authors.forename: A
authors.initials: A
authors.lastname: Gregor
authors.forename: R C
authors.initials: RC
authors.lastname: Leonard
authors.forename: D
authors.initials: D
authors.lastname: Machin
authors.forename: C G
authors.initials: CG
authors.lastname: McKenzie
authors.forename: D A
authors.initials: DA
authors.lastname: Morgan
authors.forename: J F
authors.initials: JF
authors.lastname: Smyth
authors.forename: M F
authors.initials: MF
authors.lastname: Spittle
authors.forename: R J
authors.initials: RJ
authors.lastname: Stephens
mesh_terms: D000203:Activities of Daily Living; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000532:radiotherapy*; D003131:Combined Modality Therapy / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D011879:Radiotherapy Dosage; D012074:Remission Induction
chemical_list: D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide