Neoadjuvant oxaliplatin-based chemotherapy for liver metastases from colorectal cancer. An Italian survey.

BACKGROUND: Only 10% to 25% of patients with liver metastases from colorectal cancer are suitable for resection. Methods for increasing the resectability of liver metastases are based on specific surgical techniques and neoadjuvant chemotherapy. METHODS: We collected retrospective data on patients from various Italian hospitals from 1996 to 2002. Data from colorectal cancer patients with liver metastases treated with oxaliplatin-based neoadjuvant chemotherapy were considered. Analysis focused on patients and treatment description and on longterm survival. We considered 107 patients from 36 Italian hospitals. RESULTS: Of the 105 patients assessable for response, 8.4% achieved a complete response, 70.1% a partial response and 19.6% stable disease. Ninety-nine patients were treated with surgery for liver metastases. A radical resection was achieved in 79% of patients. Median survival time was 42 months. Thirteen patients experienced grade 3-4 hematologic toxicity, and 10 patients had grade 3-4 nonhematologic toxicity. Neurologic toxicity of grade >1 was observed in 21% of patients. CONCLUSIONS: Neoadjuvant chemotherapy can be useful to increase the number of liver resections for metastatic colorectal cancer patients. Nevertheless, randomized trials are necessary to confirm this retrospective survey as well as the few single-institution experiences reported so far in the medical literature.

Safety and activity of docetaxel and trastuzumab in HER2 overexpressing metastatic breast cancer: a pilot phase II study.

We conducted a pilot phase II trial of trastuzumab administered concurrently with docetaxel in women with HER2-overexpressing advanced breast cancer. Twenty-five women with HER2-positive (3+ by immunohistochemistry = 16, 2+ = 9) metastatic breast cancer received docetaxel (75 mg/m every 3 weeks for 6 cycles) and trastuzumab (4 mg/kg loading dose, 2 mg/kg weekly thereafter). Twenty-three patients (92%) had visceral metastatic involvement. Twenty-three patients had received prior chemotherapy as part of adjuvant (18), metastatic (2), and both (3) treatment. The number of cycles administered was 121 (median 6, range 1-6). Symptomatic cardiotoxicity (GIII) occurred in one patient. The most common grade GIII/IV toxicity was neutropenia (80% of the cycles), although febrile neutropenia did not occur. No other GIII/IV toxicities were observed. Response rate was 70% (1 complete response and 15 partial responses) in 23 evaluable patients. The combination of docetaxel and trastuzumab is well tolerated and has clinically meaningful antitumor activity.

Osteonecrosis of the jaw in prostate cancer patients with bone metastases treated with zoledronate: a retrospective analysis.

Osteonecrosis of the jaw (ONJ) has recently been reported as a potentially serious complication of prolonged treatment with intravenous bisphosphonates. We studied its frequency in prostate cancer patients receiving intravenous zoledronate. The medical and dental records of 52 consecutive patients with prostate cancer and bone metastases treated at our institute between January 2002 and October 2005 were reviewed. All patients received intravenous zoledronate 4 mg every 3 or 4 weeks and concomitant conventional prostate cancer treatments. We analysed the association of ONJ with the number of administrations of zoledronate and exposure to chemotherapy. At a median follow-up of 7 months (range 1-41) after the initiation of zoledronate, ONJ occurred in six patients (12%, 95% C.I. 5.4-23.0%). All six ONJ cases occurred after the 9(th) administration of zoledronate. The median number of zoledronate administrations was 17 (range 9-24) and 8 (range 1-32) for patient developing and not developing ONJ, respectively (p =0.02). Chemotherapy with docetaxel was also associated with a strong, but not statistically significant, trend towards increased risk of ONJ (OR 3.8, 95% C.I. 0.4-35.6, p =0.24). The length of exposure to zoledronate was associated with an increased frequency of ONJ in prostate cancer patients. A possible role of chemotherapy with docetaxel as a cofactor for ONJ merits further evaluation.

Outcome of metastatic colorectal cancer: analysis of a consecutive series of 229 patients. The impact of a multidisciplinary approach.

PURPOSE: New chemotherapy agents and integrated treatments have improved the prognosis of patients with metastatic colorectal cancer. METHODS: From January 2000 to December 2002, 229 consecutive metastatic patients were prospectively followed and their outcomes were analyzed. They were divided initially into four treatment groups: A, palliative chemotherapy for extensive extrahepatic disease with or without hepatic disease (97 patients); B, palliative chemotherapy as in Group A for extensive hepatic disease unlikely to become resectable (36 patients); C, neoadjuvant chemotherapy for potentially resectable liver metastases if responsive to therapy (33 patients); D, immediate surgery for liver metastases (63 patients). RESULTS: The series was analyzed after a median follow-up of 22.6 months. The median progression-free survival was 9, 7.3, 11.5, and 26 months in Groups A, B, C, and D, respectively. The median overall survival was 20.1, 17.2, 24.8, and >48 months in Groups A, B, C, and D, respectively. The outcome was considered for the 69 patients with metastases confined to the liver (Groups B and C), who were treated initially with chemotherapy. Surgery was performed in 21 patients (5 from Group B, and 16 from Group C) and was R0 in 16. In resected patients, the median progression-free survival was 14.7 months and the median overall survival was 40.5 months. In unresected patients, the median progression-free survival was 7.6 months and the median overall survival was 17.5 months. CONCLUSIONS: Neoadjuvant therapy may prolong overall survival in a subset of patients with multiple hepatic metastases. The global impact on progression-free survival is low; less than one-half of the patients resected after chemotherapy are disease-free at three years. However, patients resected after chemotherapy obtained overall survival similar to that of primary surgery, suggesting a positive role for integrated approaches.

A phase II study of three-weekly docetaxel and weekly trastuzumab in HER2-overexpressing advanced breast cancer.

BACKGROUND: To test safety and activity of 3-weekly doses of docetaxel and a weekly dose of trastuzumab in women with HER2-overexpressing advanced breast cancer. PATIENTS AND METHODS: Forty-two women, median age 53 years (range 36-73 years), with HER2-overexpressing advanced breast cancer were enrolled in a study of docetaxel, 75 mg/m(2) q3w for 6 cycles, and trastuzumab, 4 mg/kg loading dose, 2 mg/kg weekly thereafter. Thirty-four patients (81%) had visceral metastatic involvement. Thirty-five patients had received prior chemotherapy as part of their treatment: adjuvant/neoadjuvant (26), metastatic (2) and both (7). Thirty-one patients had been previously exposed to an anthracycline and 11 to paclitaxel. Four patients had previously received high-dose chemotherapy followed by autologous stem cell transplant. RESULTS: 226 cycles (median 6, range 1-6) were administered. The median delivered dose intensity for docetaxel was 24 mg/m(2)/week (range 16-25 mg/m(2)/week). The intent to treat overall response rate was 67% (95% confidence interval, 52-79%). Median progression-free survival, time to treatment failure, and duration of response were 9, 8 and 12 months, respectively. Symptomatic cardiotoxicity (grade 3) occurred in 1 patient. The most common grade 3/4 toxicity was neutropenia (76% of the patients), although febrile neutropenia did not occur. CONCLUSIONS: Three-weekly doses of docetaxel and a weekly dose of trastuzumab is an active and safe combination in patients with HER2-overexpressing advanced breast cancer.