Sotiris K. Rigatos

Phase II Trial of Biweekly Administration of Vinorelbine and Gemcitabine in Pretreated Advanced Breast Cancer

PURPOSE To determine the efficacy of gemcitabine (GEM) plus vinorelbine (VRL) administered biweekly in pretreated patients with advanced breast cancer. PATIENTS AND METHODS Advanced breast cancer patients without response, with stable disease, or with recurrence within 6 months of prior treatment were given GEM 1,000 mg/m(2) and VRL 25 mg/m(2), once every 2 weeks for at least six cycles. RESULTS Of the 51 patients enrolled, 50 (median, age 58 years; range, 34 to 76 years) were assessable. All patients had prior chemotherapy with an anthracycline-related regimen that included taxanes in 50% of the cases. Four patients (8%) had a complete response (CR) and 23 (46%) had a partial response (PR), for an overall response rate of 54%; 16 (32%) had stable disease and 7 (14%) experienced disease progression. Response occurred mainly in patients with soft tissue (83.3%) and lung metastasis (66.7%). Response duration was 4 to 8+, 4 to 9+, and 4 to 9 months for those with CR, PR, and stable disease, respectively. The regimen was well tolerated, with grade 1 to 2 myelotoxicity and asthenia reported. No patient required a dose reduction. Gastrointestinal side effects were negligible. Patients received 99.7% (range, 93.0% to 100.0%) of the planned dose-intensity of each drug. CONCLUSION GEM in combination with VRL is an active regimen for advanced breast cancer patients, and biweekly administration significantly reduces myelotoxicity.

Effectiveness of Paclitaxel and Carboplatin Combination in Heavily Pretreated Patients with Head and Neck Cancers

A phase II study was conducted to evaluate the activity of paclitaxel and carboplatin in advanced head and neck cancer. Twenty-four patients with measurable locoregional squamous cell carcinoma and metastatic disease were entered. All had been heavily pretreated with radiotherapy, surgery and chemotherapy and were at second recurrence or disease progression when they entered the trial. Patients received Paclitaxel 200 mg/m2 with carboplatin 7 AUC once every 3 weeks with premedication with dexamethasone and diphenyldramine and ranitidine. Twenty-three patients were evaluable for response. Four patients (17%) achieved a complete response and 5 (22%) a partial response for an overall response rate of 39%. Duration of response was 3-9 months. Toxicity was tolerable. Four patients showed Grade III (WHO) and 6 Grade II neutropenia. Nineteen (79%) of patients who received more than two courses of chemotherapy presented neurotoxicity. The combination of paclitaxel and carboplatin was effective in heavily pretreated patients with squamous cell carcinoma of the head and neck.

Efficacy and tolerability of oxaliplatin plus irinotecan 5-fluouracil and leucovorin regimen in advanced stage colorectal cancer patients pretreated with irinotecan 5-fluouracil and leucovorin.

Objectives:Oxaliplatin has been introduced in the treatment of advanced colorectal cancer during the past few years. The pre-existing treatment of leucovorin–5-fluorouracil-irinotecan (IFL), although reasonably effective, has needed novel, active agents to increase the response rate and overall survival. We planned this phase 2 study in patients pretreated with IFL, adding oxaliplatin as second-line treatment: our objectives were to determine response rate and overall survival. Methods:All patients (median age 65) were designated to receive 6 cycles of chemotherapy: leucovorin 200 mg/m2 infused for 60 minutes, 5-fluorouracil 500 mg/m2 bolus at 30 minutes from the start of the previous infusion, irinotecan 135 mg/m2 infused for 90 minutes, and oxaliplatin 135 mg/m2 for 90 minutes, infused sequentially on day 1 and repeated every 3 weeks. Standard ondansetron antiemetic treatment and dexamethasone 8 mg were administered to all patients. No prophylactic recombinant human granulocyte colony-stimulating factor was permitted. Results:Fifty-seven patients were recruited and 54 were evaluable for response, survival, and toxicity. All patients had advanced, inoperable, metastatic disease in the liver and/or lungs, abdominal cavity, and multiple sites. All patients had undergone IFL pretreatment and had no response; 40 had disease progression and 14 had stable disease when entering the present study; 302 chemotherapy cycles (mean 5.92) were administered. There was no treatment delay caused by toxicity (either neutropenia or diarrhea). Irinotecan and oxaliplatin were reduced by 25% in 6 (11.1%) patients. No complete responses were observed; 21 (38.9%) patients achieved partial response, 26 (48.2%) had stable disease, and 7 (13%) had disease progression. Median duration of response was 6 months, time to tumor progression (TTP) 8 months, and median overall survival after the initiation of second-line treatment was 10 months (95% confidence interval [CI], 7.5–12.6). Conclusion:The addition of oxaliplatin to IFL as second-line treatment rendered a prolongation of survival and a response rate of 38.9% in patients in whom IFL pretreatment had failed.

Treatment of non-small cell lung cancer with gefitinib ('Iressa', ZD1839): the Greek experience with a compassionate-use program.

This is a retrospective analysis of 150 patients with advanced non-small cell lung cancer who had failed prior treatment or were unfit for chemotherapy and were treated with oral gefitinib (‘Iressa’, ZD1839; AstraZeneca) 250 mg/day. Thirty-two patients who received gefitinib for 3 weeks or less were not included in the analysis. For the remaining 118 evaluable patients, the mean age was 63.1 years; most patients had received prior chemotherapy (97.5%), Eastern Cooperative Oncology Group performance status scores 0–2 (97.4%) and stage IV disease (64.4%). The majority were symptomatic (84.6%). Disease control was observed in 30 patients (25.4%), of whom five had a partial response and 25 had stable disease; 18 (15.3%) were not evaluable. Median duration of treatment was 29.9 weeks in responding patients and 11.5 in patients with progressive disease (p<0.0001). Median overall survival was 7.3 months (15.2 months for disease control) and median progression-free survival was 3.2 months. Gefitinib was well tolerated, with grade 3/4 skin rash and diarrhea seen in 2.5 and 4.2% of patients, respectively. Clinical benefit was evaluated using questionnaires before and following treatment with gefitinib. In 82 patients with completed questionnaires, evaluation revealed symptom improvement in 40.1% and improvement in general feeling in 31.4%. Epidermal growth factor receptor (EGFR) analysis found that efficacy did not correlate with tumor EGFR overexpression. Therefore, in this retrospective analysis, gefitinib treatment provided disease control in 25% of patients who derived significant palliative benefit.

Liposomal cisplatin in cancer patients with renal failure.

7072 Background: One of the problems in chemotherapeutical agents administration is the renal failure. In general, when the grade of creatinine (and glomerular filtration data [GFR]) is of high level, chemotherapy is avoided in nearly all the cytotoxic agents or doses are reduced. Liposomal Cisplatin is a new agent, which has been tested in phase I, II, III trials and has shown no renal toxicity. In the present trial this agent was tested as a single agent and also in combination with gemcitabine mainly in lung and bladder cancer patients with renal insufficiency. Methods: 40 patients, with NSCLC 16 patients, bladder 14 and 10 with GT tract, were included. 36 were men and 4 women. Median age 65 (range 40-78). Gemcitabine was given at a dose of 1000 mg/m2 and Liposomal cisplatin 150-200 mg/m2 the first day, repeated every 2 weeks. Blood urea and serum creatinine were tested before each course of treatment and 1 week after. Full blood count was also tested the same dates. The number of courses were 6 the me...

Metastatic renal cancer and patient survival as a criterion of treatment response

Advanced metastatic renal cancer is an incurable disease, unless a successful excision of metastatic lesions can be performed. No effective treatment has yet been found. In the last few years, targeting therapies have been developed. In the past, the main treatment was based on cytokines (interferon-alpha or interleukin-2). Our objective was to determine the median and overall survival in the 66 patients who were studied and reviewed. All had histologically confirmed advanced renal cancer. There were 41 male and 25 female patients, with a median age of 60 years. In 68.18% of the patients, the treatment was mainly interferon-alpha (IFN-alpha) given 3 times a week for a median time duration of 6 months (range 3-12 months). Four patients received interleukin-2 (IL-2) and 17 patients received chemotherapy, 15 of whom had hormonal treatment. Eleven patients underwent palliative radiation therapy (in the bone or brain). Seven patients received no treatment apart from supportive care. A partial response was achieved in 11.11% of the patients treated with IFN-alpha. No response was observed in patients treated with chemotherapy or hormonal therapy. The median survival of all the patients was 20 months (95% CI 14.96-25.04). These results are discussed in comparison with the survival results of modern targeting treatment studies. In the latter studies, despite the high response rates (31-40%), the survival was 16.4 months. Our data indicate that the response rate as a criterion is not adequate in determining drug effectiveness.