Diane Logan

Oral Etoposide and Carboplatin: Effective Therapy for Elderly Patients with Small Cell Lung Cancer

PurposeElderly patients with small cell lung cancer (SCLC) and/or those with comorbid conditions are frequently not considered candidates for standard combination chemotherapy. An active, but less toxic regimen is needed for this group of patients. Patients and MethodsForty-seven elderly (>65 years) or medically unfit patients with SCLC were treated with oral etoposide 100 mg/m2 × 7 days and carboplatin 150 mg/m2 day 1. Treatment was given every 3–4 weeks for six cycles in responding patients. Patients responding to the chemotherapy regimen were also treated with prophylactic cranial irradiation, and limited-stage patients received thoracic radiotherapy. The study population included 36 extensive-stage patients and 11 limited-disease patients with renal or cardiac disease that precluded standard chemotherapy. The median age of the study population was 69 years (range: 47–84). ResultsNine of 47 patients were inevaluable for response, including four patients who succumbed to sepsis. Of the 38 patients evaluable for response, 71% responded (95% CI: 56–86%) (88% LD; 67% ED) with a complete response in 29% of patients (50% LD; 23% ED). Based on an analysis of intent to treat, the overall response rate was 60% and the median survival time of the whole group was 46 weeks (LD, 59 weeks; ED, 45 weeks). Treatment was generally well tolerated. Neutropenia was the dose-limiting toxicity; the median nadir granulocyte count was 1.04 × 109/L (range: 0–8.2). ConclusionWe conclude that this regimen can provide palliation to SCLC patients who might not otherwise be considered for systemic chemotherapy.

Breast cancer: better care for less cost. Is it possible?

OBJECTIVES To estimate the potential for cost reduction in the acute care setting and the required investment in the home care setting of implementing an outpatient/early discharge strategy for operable (stages I and II) breast cancer in Canada. METHODS Data from a community hospital were augmented by expert knowledge and incorporated into the breast cancer submodel of Statistics Canadas Population Health Model. For the estimated 90% of patients for whom this approach was assumed to be appropriate, the resource utilization for outpatient breast-conserving surgery and 2 days of hospitalization for those women undergoing mastectomy was quantified and costed, as were the appropriate home care services. A 5% readmission rate for complications was assumed. Cost per case, total cost burden, investment in home care, savings in acute care, and net savings were calculated. Sensitivity analyses were performed around readmission rates and home care/surgical follow-up costs. All costs were determined in 1995 Canadian dollars. RESULTS The cost of initial treatment for the 15,399 women diagnosed with stages I and II breast cancer in 1995 in Canada was estimated to be

Phase II study of flutamide in patients with metastatic breast cancer. A National Cancer Institute of Canada Clinical Trials Group study

127.6 million. Hospitalization made up 53% of these costs. Under the outpatient/early discharge strategy, the acute care cost of initial breast cancer management could be reduced by

Paclitaxel plus hydroxyurea as second line therapy for non-small cell lung cancer

47.2 million, with an investment in home care of

Phase II study of a one hour paclitaxel infusion in combination with carboplatin for advanced non-small cell lung cancer

14.5 million (

VP-16, ifosfamide and cisplatin (VIP) for extensive small cell lung cancer.

453 per patient), resulting in an overall net saving of

Addition of Pentoxifylline plus Nifedipine to Chemotherapy in Patients with Cisplatin-Resistant Cancers of the Lung and Other Sites

33 million. Under this strategy, hospitalization would contribute only 21% to the total care cost. CONCLUSIONS If Canadian surgeons and healthcare administrators were to work together to put in place processes to support ambulatory breast cancer surgery and if resources were redirected to the provision of home-based post-operative care, there would be potential for a large net healthcare saving and preservation of high-quality patient care.

The importance of dose intensity of doxorubicin administration in non-Hodgkin's lymphoma. A case report.

SummaryThe National Cancer Institute of Canada (NCIC) Clinical Trials Group conducted a phase II study of the oral antiandrogen flutamide in 33 patients with metastatic breast cancer. Eight patients had received no prior systemic therapy for their metastatic disease and 13 had only one site of metastasis. Toxicity occurred in 18 of the 33 patients and was primarily gastrointestinal. It ranged in severity from mild to severe with 4 patients discontinuing treatment early because of nausea, vomiting, diarrhea or stomatitis. One response, of 8 weeks duration, was noted in 29 evaluable patients. We conclude that flutamide does not have meaningful anti-tumour activity in breast cancer and plan no further trials of the drug in this disease.

Taxanes as first-line therapy for advanced non-small cell lung cancer : A systematic review and practice guideline

We tested paclitaxel (Taxol) and low dose hydroxyurea as second line therapy in 30 patients with non-small cell lung cancer since both drugs are active against non-small cell lung cancer in other settings, and since hydroxyurea may reverse chemotherapy resistance by disrupting double minute chromosomes. Hydroxyurea 500 mg was given orally each Monday, Wednesday, Friday starting 1 week before paclitaxel, and continuing until removal from study. Paclitaxel 135 mg/m2 was given i.v. over > or = 1 h every 3 weeks with dexamethasone, diphenhydramine, and ranitidine. Patients could have paclitaxel doses escalated to 175 mg/m2 in course 2 and to 200 mg/m2 in course 3, where tolerated. Sixteen males and 14 females were treated. All patients had previously received a single cisplatin-based chemotherapy regimen and 23 had previously received radiotherapy. Twelve patients had adenocarcinomas, six had squamous cell carcinomas, and 12 had large cell carcinomas. Eight patients had Stage IIIb cancers and 22 had Stage IV. Paclitaxel doses were 135 mg/m2 in 56 courses, 175 mg/m2 in 24, and 200 mg/m2 in 15. Treatment was well tolerated. Median granulocyte nadirs were 2.5 (x 10(9)/l) for paclitaxel 135 mg/m2, 1.8 for 175 mg/m2, and 1.3 for 200 mg/m2. No patient developed febrile neutropenia, and none required a dose reduction. Two patients had reversible anaphylaxis. Other toxicities were quite tolerable. They included fatigue, myalgias, dizziness, paresthesias, diarrhea, alopecia, mucositis, flushing, headache, swollen red hands, and anxiety. One patient had a partial remission and 15 had stable disease (including six with minor responses). Median survival was 20 (95% CI, 12-34) weeks, with 19% of patients remaining alive at 1 year from initiation of treatment. This is a well-tolerated regimen with modest activity as second line chemotherapy for patients with non-small cell lung cancer previously treated with cisplatin regimens. Higher doses would be feasible and other strategies are now being explored.

Practice guideline for the role of combination chemotherapy in the initial management of limited-stage small-cell lung cancer

PURPOSE To determine the activity, toxicity, and optimal dose of paclitaxel when given by one hour infusion combined with carboplatin in advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS Thirty-seven previously untreated patients with stage IIIB or IV NSCLC were enrolled. Paclitaxel was administered by one hour infusion at a dose of 175 mg/m2 for the first cycle, and was escalated up to 255 mg/m2 over successive cycles if tolerated. In the absence of toxicity, the carboplatin dose was kept constant at an area under the concentration-time curve (AUC) of 6. Cycles were repeated at 3-week intervals until progression or intolerable toxicity occurred. RESULTS Thirty-six patients were evaluable for toxicity and survival, and thirty-five for responses. The partial response rate was 10 of 35 (29%) and there were no complete responses. The median duration of response was 4.8 months (range 0.5-11.7 months). The median survival duration was 6.5 months, and 1 year survival was 31%. The mean paclitaxel dose was 188 mg/m2. Treatment was generally well tolerated. Four patients (11%) had febrile neutropenia. Five patients (14%) had grade 3 neuropathy, and 4 (11%) had grade 3 nausea and vomiting. Minor toxicities included alopecia, myalgias, arthralgias and stomatitis. CONCLUSIONS Paclitaxel and carboplatin is a well-tolerated regimen that can safely be given by a one hour paclitaxel infusion. The modest response rate observed in this study may be due to either the low dose-intensity of paclitaxel or the short infusion duration. Further trials to optimize the relative doses of paclitaxel and carboplatin are needed.