Summary A total of 610 patients with small cell lung cancer were entered into a randomised trial designed to assess the effect of duration of initial chemotherapy on survival. Patients were randomised to receive either four or eight courses of cytotoxic chemotherapy with cyclophosphamide, vincristine and etoposide and also randomised to receive, on disease progression, either second line chemotherapy ( Stopping chemotherapy early may improve the quality of life of the patients by minimising toxicity, but in responding patients may diminish survival unless further chemotherapy is effective on relapse. Although response to chemotherapy at relapse is usually clinically disappointing, Evans et al. (1985) recorded a 55% response rate with cisplatin and etoposide after previous treatment with cyclophosphamide, adriamycin and vincristine.We report here a large scale randomised trial designed to assess the effects of duration of chemotherapy on survival in patients with SCLC. The trial evaluates the effect of either 3 or 6 months' chemotherapy and then, at relapse, the effects of further chemotherapy compared with symptomatic treatment alone. Patients and methods

S_q In this single-centre study of 881 patients, S-phase fraction (SPF) was shown to be a sgnifiant prognostic marker in terms of ovrll suvival (OS), rdapse-free survival (RFS) A further stimulus to publish our data came from two recent reports which failed to find a prognostic role for SPF in breast cancer (Stanton et al., 1992; Silvestini et al., 1993

No abstract

Summary Although small cell lung cancer (SCLC) is very chemosensitive, cerebral metastases are treated with radiotherapy in the belief that they are protected from chemotherapy by the blood-brain barrier (BBB). The validity of this assumption has not been tested in clinical practice. In a randomised trial of treatment in 610 patients with SCLC, 19 patients who had symptomatic cerebral metastases at presentation were treated initially with chemotherapy, and cranial irradiation withheld. (Long et al., 1979). Indeed the increased permeability of tumour vessels to radiolabelled colloids and CT contrast media is fundamental to the radiological diagnosis of cerebral metastases. Despite this, when treating cerebral metastases it is often assumed that, because most cytotoxic drugs do not cross the intact BBB, chemotherapy will be ineffective.Even in SCLC, which is a highly chemosensitive tumour, chemotherapy has been largely ignored in the management of cerebral metastases, these patients being treated with steriods and cranial irradiation (Cox et al., 1980). There are reports of radiologically proven responses of cerebral metastases to systemic chemotherapy in SCLC (Kantarjian et al., 1984;Postmus et al., 1987; Kristiansen & Hansen, 1988) but the response rate to a single regimen is not known. However, the only systematic study of conventional chemotherapy for cerebral metastases (Rosner et al., 1986) showed that cerebral metastases from breast cancer have the same frequency of response as secondary deposits at other sites.Our aim was to assess in a prospective study the objective response rate of cerebral metastases in previously untreated SCLC patients who received uniform chemotherapy, rather than radiotherapy, as initial treatment. MethodsBetween February 1982 and September 1985, 610 patients with histologically or cytologically confirmed SCLC entered a multicentre randomised chemotherapy trial (Spiro et al., 1989). They had no past history of malignancy and had not received previous radiotherapy or chemotherapy. Brain scans were not performed routinely, and only patients with symptoms or signs of cerebral metastases at presentation had a CT or radionuclide brain scan before starting treatment. Cerebral metastases were diagnosed by the presence of enhanced lesions on CT or areas of increased uptake on isotope brain scan, compatible with the clinical findings. In these patients, cranial irradiation was withheld and initial treatment was with chemotherapy. Patients with a severe neurological deficit received oral dexamethasone, but if possible the dose was reduced during the course of chemotherapy. Steroids were not used as anti-emetics. The chemotherapy was cyclophosphamide I g m-2 i.v. day 1, vincristine 2 mg i.v. day I and etoposide 100 mg tds p.o. days 1-3. If possible the CT scan was repeated before the second cycle of chemotherapy, and it was planned that all patients be evaluated with a further scan after four cycles of chemotherapy.The study was designed to assess the response of cerebral metastases to che...

Between August 1984 and October 1987, 120 patients with stage IC to IV epithelial ovarian cancer were randomly assigned to receive carboplatin (400 mg/m2) or iproplatin (300 mg/m2) every 4 weeks as initial treatment. Stratification was made according to International Federation of Gynecology and Obstetrics (FIGO) stage and according to size of residual disease after surgery. Response was evaluated after six courses when patients were restaged, with laparoscopy or laparotomy in clinical complete responders or those with no assessable disease. Treatment was then stopped in surgically proven complete responders. Patients with partial (PR) or minor response (MR) received a further six courses of their original drug at a reduced dose (carboplatin 300 mg/m2, iproplatin 225 mg/m2). Patients with stable (SD), progressive (PD), or recurrent disease were treated with cyclophosphamide (1 g/m2). The response rates were 63% (95% confidence interval [CI], 50% to 74%) for carboplatin and 38% (95% CI, 26% to 51%) for iproplatin. Fifteen patients were not assessable for response. The median survival was 114 weeks (95% CI, 82 to 233 weeks) for carboplatin patients and 68 weeks (95% CI, 48 to 82 weeks) for iproplatin patients (P = .008). The amount of residual disease after initial laparotomy was a prognostic factor for survival. Myelosuppression was the main toxicity and was greater with iproplatin. This study shows carboplatin to be more active than iproplatin in the treatment of ovarian cancer and less toxic. Few responses to cyclophosphamide occurred following either drug, implying resistance to the alkylating agent.