The clinical activity of cyproterone acetate in advanced ovarian carcinoma. A London Gynaecology Oncology Group Study.
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Biomedical subjects
Publications and source records attributed to J Sweetenham.
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A total of 44 women received a combination of ifosfamide (1.5 g/m2 daily x5) and cisplatin (50 mg/m2 on day 1 only) as first-line chemotherapy for recurrent or metastatic carcinoma of the cervix. In all, 12/42 (38%) evaluable patients responded, with the median duration of response being 7 months. Bone marrow and gastrointestinal toxicity were frequently severe. There were 3 septic deaths. Although cisplatin plus ifosfamide is an active combination against this disease, these results suggest that it is no more so than either drug used alone.
Between March 1978 and January 1987 54 patients with advanced Hodgkin's disease (HD) or relapse following radiotherapy (RT) for Hodgkin's disease have been treated with combination chemotherapy consisting of chlorambucil, vinblastine, procarbazine and prednisolone (ChlVPP). A subgroup of five patients with bulky mediastinal disease received mantle RT in addition to ChlVPP chemotherapy. Forty-two patients (77.8%) entered complete remission with 33 (61.0%) remaining in unmaintained remission and 44 (81.5%) alive at a median follow up of 51 months (range: 22-103). The treatment was generally well tolerated with minimal toxicity. ChlVPP is effective first-line treatment for Hodgkin's disease with results which may be comparable to those achieved for MOPP but with significantly less toxicity.
Despite the high response rates induced by chemotherapy, many patients with limited small-cell lung cancer (SCLC) relapse at the site of primary disease. Failure of radiotherapy to overcome this has led to the use of surgery as part of a combined modality approach. Between December 1981 and December 1985, 189 patients with SCLC were assessed for suitability for surgery after an initial three cycles of chemotherapy (doxorubicin, cyclophosphamide, and etoposide). Fifty-seven were found to have limited disease, and of these, 19 were ineligible or unfit for surgery. Of the 38 eligible patients, 84% had an objective response to three cycles of chemotherapy and 25 were deemed suitable for surgery after restaging. At thoracotomy, four were inoperable, nine had a lobectomy, and 12 had a pneumonectomy. There was no evidence of viable SCLC in four resection specimens (one stage 1, two stage 2, one stage 3 at presentation), no viable SCLC but an entirely separate focus of viable poorly differentiated squamous carcinoma (SqLC) in one, and the remaining specimens contained viable SCLC. Survival of patients selected to undergo tumor resection was excellent (median survival, 33 months; plateau phase, 48% alive at 3 to 5 years), but survival of the entire group with limited SCLC was not dissimilar from that reported in previous series of limited-stage tumor treated with chemotherapy alone. Long-term survival appeared to be largely restricted to those with no evidence of viable SCLC at surgery (no viable SCLC, zero of five relapsed; viable SCLC, 13 of 16 relapsed and/or died). This prospective study confirms the feasibility of the combined modality approach, but suggests that any improvement in overall survival is likely to be small. Until the results from multicenter randomized trials are available, surgery, as part of a combined modality program, should be regarded as experimental.
The in vivo binding of [3H]benzo(a)pyrene (BP) and 3-[3H]methylcholanthrene (3MC) to liver and lung DNA was studied in A/J mice. Only in liver was there any reduction in total DNA-bound radioactivity between 4 h and 24 h after administration of the hydrocarbon. DNA was fractionated on Sephadex LH-20 after enzymatic digestion. A single deoxyribonucleoside-BP adduct was detected whereas two major 3MC-adducts were observed. Wtih both BP and 3MC, three additional peaks of radioactivity eluted rapidly in the lung DNA experiments while a fourth was noted with liver DNA. The nucleoside-bound adducts from lung represented a much larger proportion of the total radioactivity than with liver. In vitro analysis of 3MC binding to DNA showed the nucleoside-bound adducts to be predominantly deoxyguanosine-dependent but that the early peaks were independent of base suggesting binding to another part of the DNA molecule, perhaps phosphate, i.e, phosphotriesters.