Months Of Stable Disease Research Articles

Continuous daily administration of sunitinib in patients (pts) with cytokine-refractory metastatic renal cell carcinoma (mRCC): Updated results

5040 Background: Sunitinib malate, an oral, multitargeted tyrosine kinase inhibitor of multiple receptors, showed significant efficacy in 168 pts with cytokine refractory mRCC, with a 42% objective response rate (ORR) and progression-free survival (PFS) of 8.2 months at 50 mg/day (4 weeks on treatment, 2 weeks off) per investigator assessment (Motzer et al. JAMA 2006;295:2516–24). This study was designed to determine the efficacy and safety of single-agent sunitinib when administered in a continuous 37.5 mg/day regimen. Methods: Pts with histologically proven mRCC, refractory to a cytokine-based regimen, were enrolled in this open-label, multicenter, phase II study. Eligibility criteria included measurable disease, ECOG PS 0/1, and adequate organ function. Pts were randomized to receive sunitinib in the morning (AM) or in the evening (PM) at a dose of 37.5 mg/day, with individual doses subsequently titrated based on tolerability. The primary endpoint was RECIST-defined ORR. Secondary endpoints included PFS, adverse events (AEs) and quality of life measures. Results: 107 pts were randomized to AM (54) or PM (53) dosing and have been on study a median of 6.8 months (0.4 to 13.3). As of October 2006, 55 pts have discontinued due to progression (37 pts [35%]), AEs (17 pts [16%]), and 1 consent withdrawal (1%); 47 pts (44%) were dose reduced to 25 mg/day due to grade 2/3 AEs, the most frequent being: asthenia (12%), hand-foot syndrome (8%), and diarrhea (5%). The most commonly reported (=5% of pts) grade 3/4 AEs were hypertension (10%), asthenia (9%), hand-foot syndrome (9%), anorexia (8%), and diarrhea (6%). 31 pts (29%) were maintained on continuous sunitinib at 37.5 mg/day, and 29 (27%) were escalated to 50 mg/day. There were no significant differences between pts who received AM or PM dosing. Quality of life results will be presented. The best response by RECIST per investigator assessment shows an ORR of 19% with 43 pts (40%) with =6 months of stable disease. The median PFS is 8.3 months. Conclusions: Sunitinib 37.5 mg/day continuous dosing has a manageable safety profile and demonstrates promising clinical benefit as second-line therapy in mRCC. This regimen provides alternative sunitinib dosing that can be explored in combination studies. No significant financial relationships to disclose.

Response to chemotherapy is a major parameter-influencing long-term survival of metastatic breast cancer patients

In cancer patients, correlation between response to chemotherapy and gain in survival remains debated. We addressed this question in a multivariate analysis evaluating response to chemotherapy as a factor influencing survival of patients with metastatic breast cancer. From 1977 to 1992, 1430 patients included in eight consecutive prospective trials of anthracycline-based first-line chemotherapy in metastatic breast cancer, were available for assessment. Median follow-up was 155 months. Median survival from the date of randomisation was 24 months. Objective response rate was 63.6%. A complete response (CR) was achieved in 17% (249 patients). In a stepwise forward progression analysis objective response was the first independent prognostic factor for survival. Median survival time was 43 months for complete responders (CR), 29 months for partial responders (PR), 18 months for stable disease (SD), 5 months for progressive disease (PD). The probability of survival at 5 and 10 years was 35% and 15% for CR's and decreased to 18% and 6% for PR's. The timing of best response (at 4 or 8 months) was not related to outcome. Response to an anthracycline-based chemotherapy is a major independent prognostic factor in metastatic breast cancer. The use of this factor to investigate new drugs seems to be pertinent. The good prognosis of complete responders justifies further evaluation of new treatment strategies for this patient population.

Treatment of metastatic breast cancer with the combination of ifosfamide, epirubicin and 5-fluorouracil

An ongoing trial of combination chemotherapy using ifosfamide (Holoxan), epirubicin and 5-fluorouracil was started in 1987. A total of 30 patients with metastatic cancer of the breast received 1.5 g/m2 i.v. ifosfamide over 60 min on days 1-3, 50 mg/m2 i.v. epirubicin on day 1 and 500 mg/m2 i.v. 5-fluorouracil on day 1, followed by mesna (Uromitexan) given at 20% of the ifosfamide dose at 0, 4 and 8 h. The courses were repeated every 4 weeks. In all, 198 courses were given, ranging from 3 to 13 (median, 7) cycles/patient. The mean age of the 30 patients was 48 years (range, 35-66 years); 5 had not previously received chemotherapy and the others had failed prior cytotoxic and endocrine therapy. Overall, 28 patients were evaluable, 7 (25%) showed a complete response and 15 (54%) had a partial response, for an overall response rate of 22/28 (79%). Three patients showed stable disease with improved symptoms, and in three cases disease progression occurred. The median duration of response was 9 months (range, 3-20 months). Median survival was 11 months for all patients, 15 months for CRs, 10 months for PRs, 6 months for stable disease and 12 months for progressive disease (PD). Survival for the 22 responding patients was 12 months. Toxicity was acceptable and included alopecia, mucositis, nausea, vomiting, diarrhoea, mild cystitis and myelosuppression. Epirubicin did not appear to produce cardiac toxicity, and ifosfamide with mesna did not seem to result in severe urotoxicity. Chemotherapy with ifosfamide, epirubicin and 5-fluorouracil proved to be effective for treatment of advanced breast cancer and should be further studied in large, controlled trials.

Recombinant alpha interferon in retreatment of two patients with pulmonary lymphoma: Dramatic responses with resolution of pulmonary complications

Two patients with advanced lymphoma involving the lungs that was resistant to chemotherapy had an initial excellent response to interferon therapy. After two months of stable disease, alpha interferon A therapy was discontinued, with relapse of a few months later. Both patients had extensive pulmonary involvement with relapse of the lymphoma, and both showed a dramatic response to retreatment with alpha interferon A. Unusual interferon-related pulmonary complications were observed in one patient, and their management is detailed.

Chemotherapy of advanced prostatic cancer with adriamycin, BCNU, and cyclophosphamide.

A phase II trial of Adriamycin, BCNU, and cyclophosphamide was performed in 29 patients with advanced prostatic carcinoma (Southeastern Cancer Study Group protocol SEG 76 PR 0102P). Therapy consisted of BCNU 100 mg/m2, plus cyclophosphamide, 300 mg/m2 i.v., on day 1, followed by Adriamycin, 30 mg/m2 i.v., on day 2. Therapy was repeated every four weeks. In 27 evaluable patients refractory to prior estrogen therapy, one patient had a complete response, six patients had partial responses, and two patients had objective improvement (complete plus partial response rate 26%, and overall response rate 33%). Responders had a median time to progression of disease of 5.5 months, compared with a median time to progression of 4.0 months for those patients with stable disease. The median survival of responders was 9.3 months, compared with 6.7 months for stable disease and 3.9 months for patients with progression. Patients with higher pretreatment performance status did not have higher response rates. No life-threatening toxicity was observed. Only five patients had nadir platelet counts below 50,000/mm3, and only six patients had nadir granulocyte counts below 750/mm3. This regimen palliates the effects of hormone-resistant metastatic prostatic carcinoma.