MIC chemotherapy prolongs survival in unresectable NSCLC without compromising QOL.

Summary Twenty-seven patients cured of advanced testicular cancer by cisplatin-based chemotherapy have been assessed, a median of 30 months after start of treatment, for the long-term effects of such treatment on renal, endocrine, audiometric, reproductive and respiratory function. To control for the effects of orchidectomy on endocrine function a similar group of 11 patients cured by orchidectomy alone was also assessed. The extents of impairment in hearing and renal function were related to the total dose of cisplatin received, while the majority of patients had respiratory impairment which was, in part, related to the total dose of bleomycin. TSH was significantly higher in the chemotherapy group although serum free thyroxine and free T3 were normal in all. FSH was raised in 67% of the chemotherapy group and in 45% of the orchidectomy group while LH was raised in 75% and 45% respectively. Serum testosterone was normal in all. MethodsClinical notes were reviewed to obtain details of investigations at presentation and of chemotherapy received. Hepatic and renal function, serum TSH, free thyroxine and free T3, serum FSH, LH and testosterone, tumour markers (afetoprotein and P-human chorionic gonadotrophin) and full blood count were measured. Standard laboratory normal ranges were used and serum hormones were measured by specific immunometric methods.Pulmonary function assessment comprised measurement of vital capacity (VC), forced residual capacity (FRC), residual volume (RV), total lung capacity (TLC), forced expiratory capacity in one second (FEV,), peak expiratory flow rate (PFR), transfer factor coefficient (KCO), total lung transfer factor (TLCO), total alveolar volume (TAV) and effective alveolar volume (EAV). TLCO was measured by single breath-hold method with correction for haemoglobin concentration, EAV by single breath helium dilution and lung volumes by steady state helium dilution. Values other than TAV and EAV were expressed as standardised residuals (Miller & Pincock, 1988) with expected values determined from height and age by published regression equations (European Coal and Steel Community Recommendations, 1983

Summary Mitomycin, ifosfamide and cis-platin are three of the most active single agents in the chemotherapy of non-small cell lung cancer. We have combined them for a phase 2 study in patients with inoperable non-small cell lung cancer. The regimen ('MIC') comprised: mitomycin 6mg m -2, ifosfamide 3gm-2 and cis-platin 50mgm-2, with routine use of lorazepam, dexamethasone and high dose metoclopramide for anti-emesis. Seventy-four ambulatory patients with untreated, limited (LD) or extensive (ED) disease have entered this study, and 66 are evaluable for response. Thirty patients (45%) have achieved partial remission and 7 (11%) complete remission, as assessed radiologically. The overall response rate is thus 56% (95% confidence interval 44%-68%). There have been 29/43 responses in LD (67%, 95% CI 53%-81%) and 8/23 in ED (35%, 95% CI 15%-55%). The median response duration, measured from the start of treatment is 8.75 months. The median survival for the whole group is 9.2 months. The principal toxicity was nausea and vomiting which was severe or prolonged (>48h) for one or more courses, in 9% of patients. Performance status (PS) and weight were assessed before, and 3 weeks after the last course of chemotherapy. Fifteen (of 31 evaluable) responders improved their PS and only 1 responder deteriorated. Twenty-one of the 28 evaluable non-responders had no change in PS. The difference in PS change between responders and non-responders is highly significant (P=0.002). Thirty evaluable responders experienced a mean increase in weight of 2.9% with treatment, whereas 24 evaluable non-responders had a mean weight loss of 3.8%. This change is also highly significant (P=0.0013). MIC is clearly a well tolerated regime and among the most active combinations in non-small cell lung cancer. It will now be tested in a randomized trial against no chemotherapy.Non-small cell lung cancer (NSCLC) is the commonest malignant disease in the western world and is among the most chemoresistant. There are only 5 drugs (ifosfamide, mitomycin, cis-platin, vinblastine and vindesine) which, when tested as single agents in large numbers, produce major responses in 15% or more of cases (Kris et al., 1985). Mitomycin, ifosfamide and cis-platin have been associated with response rates of 20%, 26% and 20% respectively and are the 3 most active agents (Bakowski et al., 1983). We have combined ifosfamide with mitomycin in a recent phase 2 study in NSCLC (Chetiyawardana et al., 1985). Thirty patients were assessable for response to chemotherapy -8 achieving partial remission (PR) and 5 complete remission (CR). The overall response rate to chemotherapy was thus 43%. Cis-platin and ifosfamide have demonstrated synergism in experimental models (Goldin, 1982). Although both agents are associated with severe nausea and vomiting, a trial of anti-emetic therapy in our unit suggested that the combination of high dose metoclopramide infusion, lorazepam and dexamethasone would allow these drugs to be combined with acceptable subjective toxicity (O'Brien et al., 1987...

Since March 1980, 309 patients with anaplastic small cell carcinoma of the bronchus (ASCB) have received remission induction therapy prior to randomisation to maintenance (M) or no maintenance (NM) chemotherapy. Induction therapy consisted of six courses of vincristine, doxorubicin and cyclophosphamide (VAC) given IV every 3 weeks. Those with limited disease also received mediastinal irradiation. Consenting patients with no unequivocal residual disease were randomised to have no further treatment until relapse or a further eight courses of VAC, at a lower dosage, every 4 weeks. Patients failing to achieve randomisation status received palliative treatment only. The median survival for all patients with limited disease (LD) is 363 days and that for patients with extensive disease (ED) is 272 days (P less than 0.00001). Sixty-one patients with ED were randomised. Those having maintenance chemotherapy lived significantly longer (median 372 days) than those who did not continue therapy (median 259 days) (P = 0.006). An imbalance in the proportion of 'complete remitters' randomised to maintenance therapy does not account for this difference. There is no significant difference between the M and NM groups in the 32 randomised LD patients. Continuing treatment during remission with agents used to induce the remission can prolong survival in patients with extensive stage ASCB.

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In this multicenter study, ChlVPP/PABlOE produced results comparable to those reported for MOPP/ABVD, but with less nausea and vomiting. Treatment duration was shorter than in the original MOPP/ABVD regimen, and than that used in the Cancer and Leukemia Group B (CALGB) trial. It will now be compared with PABlOE alone.

Ifosfamide and mitomycin C are two of the more active single agents in non-small-cell lung cancer (NSCLC). This study evaluates these drugs in combination followed by radiotherapy. A total of 33 ambulatory patients with inoperable NSCLC were treated with 5 g/m2 ifosfamide as a 24-h infusion, with the concurrent administration of sodium 2-mercaptoethane sulphonate (mesna; 160% of the ifosfamide dose) and 6 mg/m2 mitomycin C given as an i.v. bolus injection on the 2nd day. The median age of the patients was 61 years. In all, 20 patients had limited disease and 13, extensive disease. A total of 30 were assessable for response to chemotherapy, 8 of whom achieved a partial response (PR) and 5, a complete response (CR) (2 were verified bronchoscopically). The overall response rate was thus 43%. All but one response (a PR) were in patients with limited disease (LD). A total of 21 patients, including 13 responders, received thoracic irradiation (30 Gy in 8 fractions over 10 days) following chemotherapy. One PR was converted to a radiological CR. In all, 17 (55%) of the patients were alive at 1 year. All patients suffered chemotherapy-induced alopecia (WHO grade 3), but there were no treatment modifications due to myelosuppression, haemorrhagic cystitis or other toxicity. WHO grade 3 nausea and vomiting were seen in all patients. There was one treatment-related death. Combination therapy using ifosfamide and mitomycin C has useful activity in NSCLC.