Fifteen-year follow-up of all patients in a study of post-operative chemotherapy for bronchial carcinoma

Abstract

Plan and conduct of the studyThe plan and conduct of the study were described in detail previously (Medical Research Council, 1971). In summary, after resection of all intrathoracic bronchial tumour, the patients were allocated at random to receive tablets of busulphan (B series), cyclophosphamide (C series), or indistinguishable placebos (P series) daily for 2 years. For the first 10 days following operation, all patients received 8 tablets in a single daily dose (B series 4 mg, C series 200 mg). Thereafter they received 6 tablets daily (B series 3 mg, C series 150 mg). However, after about the first year of intake to the study, these maintenance dosages were reduced from 6 to 3 tablets (B series 1.5 mg, C series 75 mg), because of an unexpectedly high incidence of toxicity. The 3 series were very similar with respect to sex, age, type of operation, bronchial site of tumour, histological type of tumour, and whether or not the resected lymphnodes were histologically involved.Each patient was reported on monthly during the first 3 years, 3-monthly up to 5 years, and annually thereafter. Total leucocyte and platelet counts and haemoglobin concentrations were measured every month during the first 2 years, and thereafter when requested by the clinician. The maintenance dose of tablets was controlled by the clinician from the results of the blood investigations and the dose was reduced if haematological toxicity was suspected.The study was conducted double-blind. The certified cause of death was obtained from the local centre and was verified from the death entries at the OPCS for all but 2 of the deaths.It is important to note that as the study was planned in 1964, some of the peri-operative staging procedures which would now be considered desirable were not required as a routine and when done were not necessarily reported. In particular, the following were not specifically requested as part of the protocol: recording recent weight loss, mediastinoscopy, isotope scans, liver function tests, marrow aspiration or biopsy, routine dissection of the mediastinal nodes at operation, or reporting the size of the tumour in the resected specimen.X3

Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on individual patients from 52 randomised clinical trials

“…Thirty three of these were found to be ineligible and therefore excluded (appendix 1). Of the 58 eligible trials13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 (Lung Cancer Study Group protocol 853, unpublished data; M Imaizumi, personal communication; Finnish Lung Cancer Study Group, unpublished data; European Organisation for Research and Treatment of Cancer protocol 08861, unpublished data; G Anderson, personal communication; European Organisation for Research and Treatment of Cancer protocol 08842, unpublished data; South Western Oncology Group protocol 8300, unpublished data), data were not available from six as they had been lost or destroyed or were untraceable25 26 49 50 51 52 (appendix 1). Data from 52 randomised trials and 9387 patients were therefore included in this meta-analysis.…”

Results of Pneumonectomy for Non-Small Cell Lung Cancer

“…The Lung Cancer Study Group in the USA (20) reported that postoperative radiotherapy did not increase survival rates in cases with complete resection for stages I1 and 111 squamous cell carcinoma in a randomized trial. Other studies (21)(22)(23) also showed negative results in selected patients. We could not see any beneficial effect from perioperative adjuvant radio-/chemotherapy on the prognosis in the present study (data not shown).…”

Monitoring of Nonsteroidal Immunosuppressive Drugs in Patients With Lung Disease and Lung Transplant Recipients

“…366 In a prospective 15-year evaluation of 726 patients with lung cancer treated with busulfan, cyclophosphamide, or placebo, no additional malignancies were seen in the cyclophosphamide arm above the placebo rate. 360 CHF, hemopericardium, and hemorrhagic myocarditis have been seen after high doses of cyclophosphamide. These side effects usually resolve after stopping therapy.…”

“…324,359 Table 29 summarizes the adverse events encountered with cyclophosphamide. 352,357,[360][361][362] Table 30 summarizes seven studies of cyclophosphamide for various lung diseases, 324,352,355,357,360,363,364 and Table 31 summarizes one study in which cyclophosphamide was used for nonpulmonary disease but has important information regarding toxicity. 358 3.5.2.1 Toxicity-Hemorrhagic cystitis is seen with cyclophosphamide therapy and can occasionally be severe or fatal.…”