Weekly Paclitaxel plus Capecitabine versus Docetaxel Every 3 Weeks plus Capecitabine in Metastatic Breast Cancer.

Background. We performed a randomized phase II study comparing efficacy and toxicity of weekly paclitaxel 80 mg/m(2) (Weetax) with three weekly docetaxel 75 mg/m(2) (Threetax), both in combination with oral capecitabine 1000 mg/m(2) twice daily for 2 weeks followed by a 1-week break. Patients. Thirty-seven women with confirmed metastatic breast cancer were randomized. Results. Median TTF was 174 (Weetax) versus 147 days (Threetax) (P=0.472). Median OS was 933 (Weetax) versus 464 days (Threetax) (P=0.191). Reasons for TTF were PD 8/18 (Weetax), 9/19 (Threetax); and toxicity: 8/18 (Weetax), 8/19 (Threetax). ORR was 72% (Weetax) versus 26% (Threetax) (P = 0.01). The Threetax-combination resulted in a higher incidence of leuco-/neutropenia compared to Weetax. Grade II anemia was more pronounced in the Weetax group. No difference was found in quality of life. Conclusion. Taxanes in combination with capecitabine resulted in a high level of toxicity. Taxanes and capecitabine should be considered given sequentially and not in combination.

Effects of dose-intensive chemotherapy and radiotherapy on serum n-terminal proatrial natriuretic peptide in high-risk breast cancer patients.

By using N-terminal proatrial natriuretic peptide (proANP) in serum as a marker of cardiac function, we compared the cardiac side effects of two intensive adjuvant treatment regimens for breast cancer. Patients received either 9 cycles of FEC (5-fluorouracil, epirubicin and cyclophosphamide) where the doses of epirubicin and cyclophosphamide were escalated according to the leucocyte nadir (n = 49, FEC-group) or three cycles of FEC followed by high-dose chemotherapy with alkylating agents (n = 56, CTCb-group) given with the support of peripheral blood stem cells support. Both groups received adjuvant radiotherapy. Serial measurements of proANP were performed up to three years after treatment. Mean proANP values in the FEC-group was on average 19% higher than in the CTCb-group (p = 0.002). The proANP levels showed a significant association with the cumulative dose of epirubicin (p < 0.001) but not with cyclophosphamide (p = 0.151) and 5-FU (p = 0.160). The pharmacokinetics of epirubicin was studied at the first and third chemotherapy course. The proANP levels after treatment were significantly related to the AUC (p = 0.034) and Cmax(p = 0.037) of epirubicin. Left-sided chest irradiation was associated with on average 12% higher proANP values than right-sided (p = 0.031). We conclude that dose-escalated FEC causes a stronger increase in proANP than 3 FEC followed by high-dose CTCb-treatment. Increase of proANP levels might represent an early sign of cardiotoxicity secondary to chemotherapy and radiation treatment. Long-time follow-up is necessary to determine the clinical significance of these findings.

Efficacy of pamidronate in breast cancer with bone metastases: a randomized, double-blind placebo-controlled multicenter study.

PURPOSE: To evaluate the efficacy of pamidronate 60 mg i.v. q 4 weeks in women with advanced breast cancer with skeletal metastases. PATIENTS AND METHODS: 404 woman with skeletal metastases from breast cancer in Sweden and Norway were included in a randomized, placebo-controlled, multicenter study. Except for the study medication, other palliative treatment was chosen at the discretion of the physician. Skeletal related events, i.e. increased pain, treatment of hypercalcemia, pathologic fractures of long bones or pelvis, paralyses due to vertebral compression, palliative radiotherapy for skeletal metastases, surgery on bone and change of antitumor therapy were recorded every third month as well as a self-estimated pain-score using visual Analog Scales and analgesic consumption. RESULTS: There was a significantly increased time to progression of pain (p < 0.01), to hypercalcemic events (p < 0.05) as well as for the cumulative number of skeletal related events (p < 0.01) in favor for the pamidronate group. No statistically significant reduction of pathologic fractures of long bones or pelvis, or pareses due to vertebral compression occurred. No statistically significant differences were found for the need of radiotherapy and surgery on bone. The pamidronate group faired better regarding performance status (p < 0.05). There was a statistically not significant lower consumption of opioid analgesics in the pamidronate group (p = 0.14). CONCLUSION: Pamidronate 60 mg i.v. q 4 weeks reduces skeletal events and improves the quality of life in women with bone metastases from breast cancer.

Combination chemotherapy of advanced renal cell cancer with CCNU and vinblastine.

No remission was achieved in 15 evaluable patients with measurable metastatic renal cancer treated with CCNU 120 mg/m2 (day 1) and vinblastine 0.1 mg/kg body weight (days 1 and 8) repeated every 6th week. Two additional patients were not evaluable for response owing to early death from progressive disease. Previously reported beneficial response rates in metastatic renal cancer after treatment with CCNU and vinblastine could not be confirmed.