Concurrent chemoradiotherapy followed by metastasectomy converts to survival benefit in stage IV rectum cancer.

BACKGROUND: To investigate the impact of concurrent chemoradiotherapy (CCRT) on stage IV rectum cancer. METHODS: Between 2000 and 2011, 297 consecutive patients diagnosed with stage IV rectum cancer (synchronous metastasis) were enrolled. Cox proportional hazard analyses were used for prognostic factors determination, and the Kaplan-Meier method was used for survival analyses. Propensity scores with the one-to-one nearest-neighbor matching model were used to select matched patients for validation studies. RESULTS: In total, 63 patients received CCRT and 234 did not. The patients in the CCRT group were younger, had more low-lying lesions, and had more T4 lesions, lung metastases, metastasectomies, and oxaliplatin-based upfront chemotherapy. Before propensity-score matching, a younger age (HR = 0.662, P = 0.016), lower carcinoembryonic antigen (CEA) level (≤20 ng/ml) (HR = 0.531, P = 0.001), no metastasectomy (HR = 3.214, P < 0.001), and no CCRT (HR = 1.844, P = 0.019) were independent prognostic factors after controlling for other confounding factors. After matching, only CEA and metastasectomy, but not CCRT, were independent prognostic factors. The survival benefit of CCRT was restricted to patients who undergo subsequent metastasectomy. CONCLUSIONS: Upfront CCRT only provided a survival benefit in patients with stage IV rectum cancer who undergo subsequent metastasectomy.

Adjuvant oxaliplatin- or irinotecan-containing chemotherapy improves overall survival following resection of metachronous colorectal liver metastases.

PURPOSE: Adjuvant systemic 5-fluorouracil (5-FU)-based chemotherapy improves survival after resection of synchronous colorectal liver metastases (CLMs), but not metachronous. We retrospectively examined if adjuvant chemotherapy with new regimen containing oxaliplatin or irinotecan improved survivals after resection of metachronous CLMs. METHODS: Between 2000 and 2007, 52 patients having undertaken resection of metachronous CLMs with curative intent were identified from Taipei Veterans General Hospital hospitalization registry. One patient with perioperative mortality and another being lost to follow-up within 3 months after metastasectomy were excluded. Thirty-one patients experienced six to 12 cycles of FOLFOX or FOLFIRI chemotherapy while 19 patients with 5-FU/leucovorin (LV)-based chemotherapy following CLM resection. The primary end point was disease-free survival (DFS) and secondary end point, overall survival (OS). RESULTS: By the univariate analysis, median DFS was 34.3 months in the FOLFOX/FOLFIRI group vs 14.2 months in the 5-FU/LV group (P = 0.022). The median OS and 5-year survival rates were longer than 57.7 months (not reached, with median follow-up of 35.5 months) and 54.0%, respectively, in the FOLFOX/FOLFIRI group compared to 49 months and 34.6% in the 5-FU/LV group (P = 0.027). FOLFOX/FOLFIRI chemotherapy was shown by multivariate analyses to be an independent factor predicting a better DFS (hazard ratio [HR] = 0.37; 95% CI: 0.15-0.94; P = 0.036) and a better OS (HR = 0.27; 95% CI: 0.083-0.86, P = 0.026) than 5-FU/LV-based. CONCLUSIONS: Adjuvant FOLFOX/FOLFIRI chemotherapy following resection of metachronous CLMs is demonstrated to have better DFS and OS than 5-FU/LV chemotherapy.

Oxaliplatin added to simplified bimonthly low-dose leucovorin and 5-FU for pretreated advanced colorectal cancer is effective and not affected by different previous 5-FU regimens.

This phase II study examined bimonthly oxaliplatin (85 mg/m2) added to a continuous infusion of fluorouracil (3000 mg/m2 for 46 h following a 400 mg/m2 bolus), with leucovorin (LV) (150 mg/m2) administrated in a simplified way to patients with metastatic colorectal cancers (CRC) refractory or resistant to 5-fluorouracil (5-FU). Sixty patients were registered. Of the 52 evaluable patients, 3 (5.8%) achieved a complete response (CR) and 18 (34.6%) achieved a partial response (PR). The overall response rate (CR + PR) was 40.4% (95% confidence interval [CI]: 26.6%-54.2%) for evaluable patients and 35% (95% CI: 22.6%-47.4%) by intention to treat. The median progression-free survival (PFS) was 5.2 months, and the median survival was 14.2 months. No significant differences were seen in response rates and PFS of patient groups pretreated either with high-dose 5-FU/LV by continuous infusion or with intravenous 5-FU/LV by a weekly bolus. From the 421 cycles analyzed, dose-limiting toxicities included cumulative sensory neuropathy and leukopenia, accounting for 11.6% and 10.0%, National Cancer Institute-Common Toxicity Criteria grade 3/4 toxicities per patient, respectively. Two (3.3%) patients experienced hepatic encephalopathy related to high-dose 5-FU. With necessary caution, this regimen was effective for 5-FU-pretreated CRC, regardless of ethnic differences, and it had the advantage of LV being administrated at a low dose in a simplified way.

Irinotecan (CPT11) plus high-dose 5-fluorouracil (5-FU) and leucovorin (LV) as salvage therapy for metastatic colorectal cancer (MCRC) after failed oxaliplatin plus 5-FU and LV: a pilot study in Taiwan.

BACKGROUND: Irinotecan (CPT11) has established activity against advanced colorectal cancer without cross-resistance with 5-fluorouracil + leucovorin-based therapy. We conducted this pilot study to evaluate the efficacy and tolerance of combination treatment with irinotecan and 5-fluorouracil (5-FU) for patients in whom combination treatment with oxaliplatin with 5-FU + leucovorin has failed. METHODS: Patients were enrolled in this study after oxaliplatin treatment had failed. The treatment protocol consisted of CPT11 (180 mg/m(2) for 90 min) on day 1 and a 2 h infusion of 200 mg/m(2) leucovorin followed by 400 mg/m(2) 5-FU as an intravenous bolus injection plus a 22 h continuous infusion of 600 mg/m(2) 5-FU. This regimen was repeated for two consecutive days every 2 weeks. RESULTS: A total of 18 patients were eligible for this study and in total 144 cycles of therapy (median eight cycles) were given to these patients. Four patients (22.2%; 95% CI: 8-36.4%) achieved an objective response of partial remission (PR) and an additional seven obtained stable disease (SD) status or minor response. The median duration of response was 8 months and 14 patients were alive at the end of the study. Hematological toxicity (neutropenia) was the most common serious side effect (29.2%), followed by gastrointestinal effects (diarrhea, 28.5%). Grade II-III diarrhea was experienced for at least one cycle by each patient. CONCLUSIONS: The results of treatment for patients after oxaliplatin failure are encouraging and this treatment protocol is also well tolerated by previously heavily treated patients.