Jones Wg

Importance of bleomycin in combination chemotherapy for good-prognosis testicular nonseminoma: a randomized study of the European Organization for Research and Treatment of Cancer Genitourinary Tract Cancer Cooperative Group.

PURPOSE This prospective randomized trial was designed to compare the efficacy of etoposide plus cisplatin (EP) versus bleomycin, etoposide, and cisplatin (BEP) chemotherapy in patients with good-prognosis metastatic nonseminomatous testicular cancer. PATIENTS AND METHODS Four hundred nineteen patients with good-prognosis nonseminomatous testicular cancer were randomized to receive four cycles of cisplatin 20 mg/m2 on days 1 to 5 plus etoposide 120 mg/m2 on days 1, 3, and 5 with or without bleomycin 30 mg weekly. RESULTS Of 395 eligible patients, 169 of 195 patients allocated to EP (87%) and 189 of 200 patients allocated to BEP (95%) achieved a complete response with chemotherapy alone or after postchemotherapy surgery. These results are significantly different (P = .0075). After a median follow-up duration of 7.3 years, eight patients (4%) on each treatment arm relapsed. In view of the low number of unfavorable treatment outcomes (11%), no significant differences were detected in time to progression (P = .136) and survival (P = .262). Both the acute and late pulmonary toxicity and neurotoxicity were significantly greater in patients who received BEP, whereas Raynauds phenomenon occurred exclusively in patients who received BEP (P < .001). Two patients treated with BEP died of bleomycin pulmonary toxicity. CONCLUSION BEP is the most effective combination regimen in the treatment of disseminated nonseminomatous germ cell cancer. In this particular BEP regimen with etoposide at a dose of 360 mg/m2 per cycle, even in good-prognosis patients, bleomycin cannot be deleted without compromising treatment efficacy, but its use is associated with more toxicity (particularly pulmonary) and efforts to reduce this merit further exploration.

Long-term follow-up of non-seminomatous testicular cancer patients with mature teratoma or carcinoma at postchemotherapy surgery

From 1979 to 1983 the EORTC GU Group treated 239 patients with disseminated non-seminomatous testicular cancer with combination chemotherapy comprising cisplatin, vinblastine and bleomycin in a prospectively controlled trial. The protocol required complete resection of residual masses after induction chemotherapy, provided that serum tumour markers were normal. 102 patients were operated on. 27 patients had mature teratoma (teratoma differentiated) in the resected specimens and 23 had viable cancer. Follow-up data were available for 26 and 22 of these patients, respectively. 23 of 26 patients (88%) with mature teratoma are alive and disease free after a follow-up of 53-110 months (median 92 months). 3 patients developed progressive disease; 1 died. A peculiar case of growing mature teratoma on the forearm is described. 13 of 22 patients (59%) with residual carcinoma are alive and disease free after a follow-up of 74-112 months (median 95 months). The prognosis of patients with carcinoma is shown to be correlated with the completeness of surgery, which in turn is correlated with the initial tumour mass before chemotherapy.

Effective palliation of advanced breast cancer with weekly low dose epirubicin

A single institution Phase II study of weekly low dose epirubicin was performed on patients with advanced breast cancer. They received epirubicin in doses approximating to 12 mg/m2 i.v. each week. Most patients had received prior hormone therapy and five had previous chemotherapy; all were post-menopausal. Only patients with bidimensionally measurable visceral or soft tissue metastatic lesions were eligible for objective assessment of response according to WHO criteria. Forty-two patients were evaluable for response and 46 were evaluable for toxicity. An objective response rate of 43% was observed (95% CI = 27.9-57.8%) confirming that epirubicin is an active single agent in breast cancer. Remarkably little toxicity was seen; 35% of patients reported no toxicity at all. Since this low dose weekly approach was so well tolerated, and yet was effective, useful palliation was achieved in this group of patients.

Sister chromatid exchanges in human lymphocytes exposed to single cytotoxic drugs in vivo or in vitro

Venous blood was taken from apparently healthy volunteers and patients with cancer, the latter both before and at intervals after treatment with single cytotoxic drugs. Cells from untreated individuals were exposed to a range of concentrations of drugs in culture medium. Chlorambucil, treosulfan and cyclophosphamide (activated by hepatic microsomes) significantly increased the numbers of SCEs, both in vitro and in the lymphocytes of patients. While methotrexate and 5-fluorouracil had no effect, bleomycin slightly increased the number of SCEs, but only in vitro. Although the in vitro dose-effect relationship indicated which drugs would increase the frequency of SCE in vivo, the magnitude of the response tended to be overestimated. When patients were treated with drugs the frequency of SCE increased, then declined with time. Though this complicates the quantitative relationship between dose and damage, SCEs may be useful to monitor the effects of alkylating agents on normal tissues.

The quantitation of sister chromatid exchanges in lymphocytes of cancer patients at intervals after cytotoxic chemotherapy

Venous blood was taken from patients with cancer, prior to and up to 42 days after the administration of cytotoxic chemotherapy. Lymphocytes were stimulated to divide in vitro, and examined for sister chromatid exchanges (SCEs). Cyclophosphamide rapidly increased the frequency of SCE, which returned to approximately double the control value 24 hr after administration. The remaining SCEs disappeared more slowly. There was a positive correlation between the dose of drug and the frequency of SCE measured immediately and 4 hr, 20 hr and 21 days after treatment. As patients received successive courses of treatment the number of SCEs generally increased from about 0.14 to 0.25 per chromosome. After this, further chemotherapy was often less effective in inducing them. The presence of SCEs in peripheral blood lymphocytes may be a useful indicator for the occurrence and persistence of alkylating metabolites, residual damage in the DNA and individual responses of patients to a standard regimen.