A phase II study of cetuximab/irinotecan in patients with heavily pretreated metastatic colorectal cancer: predictive value of early specific toxicities.

BACKGROUND: This study was designed to evaluate the predictive value of early specific toxicities on efficacy of weekly irinotecan/cetuximab administered as salvage therapy in patients with metastatic colorectal cancer (CRC) refractory to oxaliplatin and irinotecan. PATIENTS AND METHODS: Seventy patients received a regimen composed of weekly irinotecan 125 mg/m2 as a 1-hour intravenous infusion and cetuximab 400 mg/m2 infused over 2 hours as the initial dose and 250 mg/m2 infused over 1 hour for subsequent administrations. A single treatment cycle was composed of 4 weekly irinotecan infusions followed by 2 weeks of rest. The predictive value of adverse events (AEs) attributable to cetuximab (rash) and major toxicities attributable to irinotecan (gastrointestinal [GI] and hematologic) were observed after the first cycle of treatment and, therefore, correlated to activity and efficacy of cetuximab and weekly irinotecan. RESULTS: Sixty-six of 70 patients received >or= 1 cycle of chemotherapy and were therefore evaluable for response. Overall, toxicity observed was generally mild and manageable. According to an intent-to-treat analysis, a partial response was exhibited in 15.7% of patients, with a median progression-free survival (PFS) and median overall survival time of 4 months and 9 months, respectively. As expected, PFS (P = .01) and median survival (P = .04) correlated strongly with the presence and severity of the rash. Surprisingly, the presence of at least moderate hematologic and GI toxicity was associated with improved PFS (P = .03). CONCLUSION: Our data suggest that irinotecan-induced AEs might predict a better outcome in advanced CRC. This finding would identify a different subset of patients-those likely to benefit from a renewed sensitivity to irinotecan induced by cetuximab.

Adjuvant chemotherapy in muscle-invasive bladder carcinoma: a pooled analysis from phase III studies.

BACKGROUND: The treatment of muscle-invasive bladder carcinoma should include both the eradication of local disease and the elimination of potential micrometastases. To date, the 'gold standard' treatment for muscle invasive bladder carcinoma has been recognized to be radical cystectomy. Adjuvant chemotherapy (AC) has the advantage of being administered to patients with known prognostic factors of recurrence. A pooled analysis was used to verify whether AC is able to increase the disease-free survival (DFS) and overall survival (OS) of patients with muscle-invasive bladder carcinoma who had undergone radical cystectomy. METHODS: All published randomized Phase III studies were considered eligible and a literature-based pooled analysis was accomplished. DFS and OS were the endpoints. Event-based relative risk ratio (RR) and 95% confidence intervals (95% CI) were derived. Combined effect estimation was computed with a fixed- and a random-effect model. A heterogeneity test was applied as well. RESULTS: Five trials were collected. All were evaluable for OS (350 patients) and four of these also were evaluable for DFS (273 patients). A significant benefit from AC was noted both in OS (RR, 0.74; 95% CI, 0.62-0.88 [P = 0.001]) and DFS (RR, 0.65; CI 0.54-0.78, [P < 0.001]). No significant heterogeneity was found. CONCLUSIONS: Although the results of the analysis favor the use of AC, larger studies are needed to identify the role of AC in the treatment of muscle-invasive bladder carcinoma. Ongoing trials (European Organization for Research and Treatment of Cancer [EORTC]/Southwest Oncology Group [SWOG] and the Italian Multicentric Study) can help to better identify patients who can benefit from this approach.

Long-term survival in locally advanced oral cavity cancer: an analysis of patients treated with neoadjuvant cisplatin-based chemotherapy followed by surgery.

BACKGROUND: Neoadjuvant chemotherapy has been reported to be extremely active in head and neck cancer but has failed to give a statistically significant improvement in survival. METHODS: From 1981 to 1994, 33 operable patients with locally advanced oral cavity cancer received cisplatin-based chemotherapy before surgery. Postoperative radiotherapy was performed in high-risk patients. RESULTS: The overall clinical and pathologic complete response rates to neoadjuvant chemotherapy were 48% and 30%, respectively. At a median follow-up of 7.0 years (range, 0.3-15.3+ years), the 5-year and 10-year overall survival rates were 54.5% and 39.5%, and the disease-specific median survival was 6.6 years for all patients (8.3 and 2.3 years for stages III and IV, respectively). The univariate analysis showed a positive relationship between survival and male sex (p = .05), pathologic (p = .02), and clinical (p = .03) complete response. The Cox proportional hazard regression model confirmed the independent prognostic value of the clinical response with a 4.67 (95% CI, 1.70-12.86) hazard ratio. A second primary tumor occurred in six patients (18%), with a median of occurrence of 9 years (range, 7-11 years). CONCLUSIONS: This study confirms the prolonged survival expectancy largely exceeding 5 years for selected patients with stage IV and for most with stage III locally advanced oral cavity cancer achieving a clinical and/or pathologic complete response to chemotherapy.

Single colon metastasis from breast cancer: a clinical case report.

Metastatic involvement of the extrahepatic digestive system is rare. We here report the case of a 62-year-old woman who presented with a bowel obstruction related to a metastasis of breast cancer occurring 12 years after a mastectomy for lobular carcinoma. No other distant metastases were detected except for two nodules of 20 and 5 mm on the right chest wall. Biopsy of the larger nodule showed a lobular carcinoma. The patient underwent a right hemicolectomy and then received chemotherapy combined with letrozole, resulting in a partial response. The literature revealed only a few cases of breast cancer metastatic to the colon. Patients with known breast cancer, particularly of the lobular histological type, who present with specific or less specific abdominal symptoms or signs such a microcytic anemia, should be endoscopically explored in order to detect possible metastases of the primary breast tumor.