Gemcitabine in the treatment of refractory Hodgkin's disease: results of a multicenter phase II study.

PURPOSE: To explore the use of gemcitabine for the treatment of patients with relapsing or refractory Hodgkin's disease. PATIENTS AND METHODS: Eligible patients had measurable disease and more than one previous chemotherapy regimen. Patients previously treated with high-dose chemotherapy with autologous bone marrow or peripheral stem-cell support were not included. Gemcitabine, 1,250 mg/m(2), was administered as a 30-minute intravenous infusion on days 1, 8, and 15 of each 28-day cycle of therapy. The dosing schedule remained fixed, and any dose of gemcitabine that could not be given on time was omitted. Patients who had not experienced any hematologic or nonhematologic toxicity after one complete cycle of therapy were permitted to have subsequent doses increased by 20%: that is, from 1, 250 mg/m(2) to 1,500 mg/m(2). RESULTS: Of the 23 enrolled patients, 22 were assessable for response; all 23 patients were included in the efficacy analysis. Disease status for two patients (9%) reached a state of complete remission, and seven patients (30%) achieved a partial response, for an overall response rate of 39% (95% confidence interval, 19.7% to 61.5%). The likelihood of achieving a response was not influenced by a patients' main pretreatment characteristics or by their response to their last prior chemotherapy. The median duration of response was 6.7 months (range, 2 to 33+ months), and the median overall survival time was 10.7 months (range, 4 to 34.7+ months). In general, toxicities were mild; no treatment-related deaths occurred, and only one life-threatening adverse event was reported for this study. CONCLUSION: Gemcitabine was shown to be active in heavily pretreated patients with Hodgkin's disease, producing a response rate of 39%. Additionally, drug-related toxicities were mild, which thus suggests the possible inclusion of gemcitabine in an earlier phase of treatment.

A summary of the Milan experience with multimodality therapies in patients with small cell lung cancer: attempts to improve long-term outcome.

From February 1985 to June 1993, 173 consecutive, previously untreated patients with small cell lung cancer received individualized treatment tailored to disease extent. Almost all patients (14 of 16) with stage I and II disease and 30 patients with operable stage III disease were submitted to surgery preceded or followed by chemotherapy. Chest irradiation and prophylactic brain radiotherapy (in complete responders) were administered at the end of treatment in 42 of 44 cases. Patients with inoperable limited disease received chemotherapy followed by radiotherapy in 67 of 71 cases, while chemotherapy alone or followed by radiotherapy in sites of either initially bulky or residual disease was administered to 58 patients with extensive disease. The overall response rate was 77% (complete response, 45%; partial response, 32%). Complete responses were documented more frequently in limited disease than in extensive disease (57% v 22%; P < .001). The 2- and 5-year freedom from progression rates (24% and 16%, respectively), as well as overall survival rates (31% and 16%, respectively) were significantly affected by disease extent. No patient with extensive disease was progression free and alive at 2 years, while more than half of stage I and II patients were disease free and alive at 5 years. This retrospective analysis performed on a large number of consecutive, nonrandomized patients suggests that, at least in patients with limited disease, it is possible to achieve favorable long-term results using treatment tailored to disease extent. Nonetheless, the disappointing results commonly achieved in the treatment of small cell lung cancer strongly support the need for either prospective, randomized studies to confirm recently reported improved results or new pilot studies with investigation of entirely innovative approaches.

Single-agent chemotherapy with vinorelbine for pretreated or metastatic squamous cell carcinoma of the esophagus.

AIMS AND BACKGROUND: At least half of the patients with squamous cell carcinoma of the esophagus (SCCE) present at diagnosis with metastatic disease, and most patients in a locally advanced phase will develop metastases despite potentially curative local therapy. Thus, the majority of patients with SCCE will become candidate for palliative chemotherapy. Only a few drugs have demonstrated moderate activity (>15%) against SCCE. The main purpose of this phase II trial was to assess the activity of vinorelbine, a semisynthetic vinca alkaloid with a wide spectrum of action, in advanced or relapsed SCCE. METHODS: Seventeen patients were included in the trial. Eleven of them had already received chemotherapy (cisplatin and fluorouracil) and/or radiotherapy at the time of the first diagnosis. All patients were treated with vinorelbine at the dose of 30 mg/m2 every two weeks. RESULTS: Sixteen of the 17 patients enrolled in the trial were assessable for activity: partial responses were observed in 4 of the 16 (25%), and 3 of them were pre-treated patients. A significant improvement of dysphagia was obtained in 4 of 11 symptomatic patients. Toxicity was mild, with only one episode of grade 4 neutropenia and constipation. CONCLUSIONS: In our experience, single-agent vinorelbine is active against SCCE. It was also active in patients previously treated with cisplatin and fluorouracil. The good tolerability and the possibility of relieving symptoms such as dysphagia strongly suggest the addition of vinorelbine to combination regimens with cisplatin as front-line chemotherapy for SCCE.

Analysis of epidermal growth factor receptor expression as a predictive factor for response to gefitinib ('Iressa', ZD1839) in non-small-cell lung cancer.

Gefitinib ('Iressa', ZD1839) is an orally active epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that has demonstrated antitumour activity and favourable tolerability in Phase II studies. We investigated whether EGFR expression levels could predict for response to gefitinib in patients with advanced non-small-cell lung cancer (NSCLC), who received gefitinib (250 mg day(-1)) as part of a worldwide compassionate-use programme. Tissue samples were analysed by immunohistochemistry to assess membrane EGFR immunoreactivity. Of 147 patients enrolled in our institution, 50 patients were evaluable for assessment of both clinical response and EGFR expression. The objective tumour response rate was 10% and disease control was achieved in 50% of patients. Although high EGFR expression was more common in squamous-cell carcinomas than adenocarcinomas, all objective responses were observed in patients with adenocarcinoma. Response and disease control with gefitinib were not associated with high EGFR expression. Overall, median survival was 4 months, and the 1-year survival rate was 18%. Strong EGFR staining correlated with shorter survival time for all patients. Gefitinib demonstrated promising clinical activity in this group of patients with NSCLC. These results have also shown that EGFR expression is not a significant predictive factor for response to gefitinib.

Combined regimen of cisplatin, doxorubicin, and alpha-2b interferon in the treatment of advanced malignant pleural mesothelioma: a Phase II multicenter trial of the Italian Group on Rare Tumors (GITR) and the Italian Lung Cancer Task Force (FONICAP).

BACKGROUND: The cisplatin-doxorubicin combination has shown moderate activity in malignant pleural mesothelioma (MPM; objective response, 25%), and preclinical studies suggest that interferons (IFNs) may have an antiproliferative effect on mesothelioma cell lines with a marked increase in cisplatin cytotoxicity. Therefore, the combined chemoimmunotherapy regimen is an worthwhile approach to evaluate in a Phase II trial. METHODS: From December 1995 to June 1999, 37 previously untreated patients with MPM were treated with cisplatin 60 mg/m(2) intravenously on Day 1 plus doxorubicin 60 mg/m(2), recycled every 3-4 weeks and IFN-alpha-2b, 3 x 10((6)) international units subcutaneously 3 times a week for a total of 6 courses or until progression. Inclusion criteria were histologic diagnosis of MPM and measurable disease defined by computed tomography scan or magnetic resonance imaging. RESULTS: Thirty-four patients were assessable for toxicity and 35 for efficacy according to World Health Organization criteria. One hundred thirty-five courses were administered with a median of 4 cycles per patients. Seventy-six percent of patient presented at least 1 episode of severe myelosuppression (Grade 3 and 4). Severe anemia and thrombocytopenia occurred in 30% and 24% of patients, respectively. Sixty percent of patients presented constitutional symptoms. In the 35 patients assessable for response, the overall response rate was 29% (95% confidence interval, 15-47%). The median duration of response was 8.4 months. With a median follow-up of 19.6 months, the median survival was 9.3 months. One- and 2-year survival was 45% and 34%, respectively. CONCLUSIONS: This combined regimen has definite activity in MPM. However, toxicity, particularly myelosuppression and fatigue, is not negligible and may limit its application.