Combination chemotherapy with cisplatin, vindesine and mitomycin-C for advanced, inoperable non-small-cell lung cancer.

OBJECTIVES: To assess the activity of chemotherapy with cisplatin, vindesine and mitomycin-C (PVM) in advanced non-small-cell lung cancer (NSCLC) and to test the feasibility of preemptive therapy with PVM. DESIGN AND SETTING: A phase II clinical trial of PVM in patients with NSCLC treated at the Royal Prince Alfred Hospital between June 1987 and July 1990. PATIENTS: Forty-one patients with advanced, inoperable or recurrent NSCLC--22 women, 19 men, with a median age of 51 years. Thirteen patients had been treated previously with radiotherapy and/or surgery; 18 had extrathoracic metastases. Four patients previously deemed inoperable were treated preemptively with PVM before proceeding to radical surgery. INTERVENTIONS: Cisplatin 100 mg/m2, vindesine 5 mg and mitomycin-C 8 mg/m2, all given intravenously on Day 1, with vigorous hydration and antiemetic therapy. Cycles were repeated every four weeks. MAIN OUTCOME MEASURES: Objective tumour response to treatment, patient survival time, time to treatment failure, and treatment toxicity. RESULTS: There was one complete tumour response to PVM and 15 partial responses; 14 patients had stable disease and nine had progressive disease--yielding an objective response rate (complete plus partial responses) of 39% (16/41; 95% confidence interval [CI], 24%-56%). Responses were documented in all histological subgroups, in both locally advanced and disseminated disease, and in recurrent disease. Median survival of the group was six months (95% CI, 5-10 months; range, 0.5-19+ months), and is unchanged by exclusion of the four patients treated before surgery. Seven of the 41 patients (17%) survived 12 months or longer. Median time to treatment failure in patients who had an objective response was six months (95% CI, 5-10 months). Grade 3 or 4 nausea and vomiting occurred in 21 patients (51%). Haematological, renal and neurological toxicity were not major problems; there were no deaths from treatment toxicity. CONCLUSION: PVM is an active regimen in advanced NSCLC and can produce durable remissions. The potential palliative effects of PVM in incurable disease must be weighed against the risk of subjective toxicity.

Retrospective review of chemotherapy for small cell lung cancer in the elderly: does the end justify the means?

Between 1978 and 1983, 72 patients aged 70 years or older (median 72, range 70-80) were treated for biopsy-proven, small cell lung cancer (SCLC). Intercurrent disorders were common, including ischaemic heart disease, peripheral vascular disease, chronic airflow limitation and second malignancies. 26 patients (36%) had limited extent of disease, and 46 (64%) had extensive disease. "Intensive" chemotherapy incorporating vincristine, cyclophosphamide and doxorubicin (OCA regimen) was administered to 32 patients [complete response (CR) + partial response (PR) = 84%]; less rigorous regimens (e.g. single agent chemotherapy, planned dose reductions, radiotherapy only) were used in 34 cases (CR + PR = 52%); and 6 received no active treatment. In the intensively treated group, there were 3 treatment-related deaths and 26 episodes of WHO grade 3-4 toxicity. In the less intensively treated group, there were no treatment-induced deaths and only 1 episode of severe toxicity. The overall median survival was 25 weeks (36 weeks for intensive treatment, 16 weeks with less intense treatment). For patients with limited disease only, the median survival in each group was 43 and 26 weeks, respectively. Intensive treatment for elderly patients with small cell lung cancer is associated with substantially increased toxicity and higher response rates than for gentle treatment, but without a major survival benefit.

Phase II trial of carboplatin in the management of malignant mesothelioma.

Thirty-one patients with advanced malignant mesothelioma, previously untreated or having received only one prior cytotoxic regimen, were treated in a prospective, single-arm phase II trial with carboplatin (NSC 241240) at a dose of 150 mg/m2 per day intravenously (IV) for 3 days (450 mg/m2/course). One complete remission and four partial remissions were achieved, yielding an overall objective response rate of 16% (95% confidence interval [CI], 5.4% to 34%). The median duration of remission was 8 months (range, 5 to 17). Nonhematological toxicity was mild (only 12% with World Health Organization [WHO] grade 3 vomiting); 16% suffered WHO grade 3 to 4 hematological toxicity, but there were no life-threatening episodes and no treatment-related deaths. Carboplatin has modest activity against malignant mesothelioma and, because of its low toxicity, has a role in the management of this disease.

Carboplatin (CBDCA, JM-8) and VP-16-213 in previously untreated patients with small-cell lung cancer.

The efficacy and toxicity of carboplatin 100 mg/m2, administered intravenously (IV) daily X 3, and VP-16-213 120 mg/m2, IV daily X 3, administered every 28 days for six courses, was assessed in 94 (36 limited stage, 58 extensive stage) previously untreated patients with small-cell lung cancer. Mediastinal irradiation using 50 Gy in 25 fractions was given to all limited-stage patients with a complete (CR) or partial response (PR) after three chemotherapy courses. Cranial irradiation was administered to all patients with CR. Objective responses were seen in 77% (CR 40%, PR 37%) of patients with limited-stage and 58% (CR, 9%; PR, 49%) with extensive-stage disease. Median relapse-free survival for objective responders with limited stage was 14.6 months and 7.9 months for extensive-stage patients. Median relapse-free survival following CR was 15.4 months and 8.5 months for PR. Median survival was 15.3 months for limited-stage and 8.1 months for extensive-stage patients. The combination was well tolerated with mild nausea or less (World Health Organization [WHO] grade 0 or 1) in 62% of patients and minimal mucositis, renal, neurotoxicity, or ototoxicity. Neutropenia less than 1.0 X 10(9)/L (WHO grade 3 or 4) was seen in 63% of patients, with two deaths from infection while neutropenic. The combination of carboplatin and VP-16-213 is a new, active program with low toxicity when applied intensively in previously untreated patients with small-cell lung cancer.

Surgical treatment of bullous emphysema.

Between 1974 and 1981, 20 patients had surgical treatment for bullous emphysema. There were 15 males and five females with a mean age of 40 years. The majority of patients had symptomatic respiratory disease, were smokers and had a past history of lung disease. In all cases bullae were visible on chest X-ray, the primary diagnostic investigation, and simple spirometry was used to assess lung function pre- and postoperatively. Cyst resection was performed in 14 cases (two bi-laterally) and pleurodesis was added in six of these cases. Lobectomy was performed in four patients and in two a pedunculated cyst was simply ligated and excised. There were no deaths and morbidity was acceptably low. Vital capacity (VC), Forced expiratory volume in 1 s (FEV1) and FEV1:VC ratio were all significantly improved with surgery though the correlation of subjective and objective results was variable. Surgery is appropriate for symptomatic patients with bullae visible on chest X-ray and asymptomatic patients with rapidly enlarging bullae occupying more than 30% of a hemithorax.

Immunoblastic lymphoma in husband and wife.

Cases of an identical diffuse immunoblastic lymphoma in husband and wife are reported. The disease was fatal in both cases, deaths occurring within weeks of each other, and similar clinical characteristics were present in both patients.

Pulmonary alveolar--septal amyloidosis associated with pulmonary tuberculosis and an unusual paraproteinaemia.

A patient is described who presented with mixed obstructive and restrictive lung disease, shown to be due to deposition of amyloid in an alveolar-septal distribution. An association with a plasma cell dyscrasia and pulmonary tuberculosis is discussed, as is the need for early diagnosis and a trial of aggressive cytotoxic therapy in primary amyloidosis.

Uterine fibroid: an unusual cause of recurrent haemorrhagic pleural effusion.

A 51-year-old woman presented with dyspnoea due to pleural effusion, which repeatedly reaccumulated rapidly after tapping. A pelvic mass was present and she was considered to have disseminated ovarian malignant tumour. Total hysterectomy with bilateral salpingo-oophorectomy was performed, and the tumour was shown to be a necrotic uterine fibromyoma. After the operation the patient has been well, with no recurrence of the effusion. This is the twelfth reported case of the association of hydrothorax with uterine fibromyoma, and is a form of the rare pseudo-Meigs' syndrome.