Multicenter phase II study of biweekly CAPIRI plus bevacizumab as second-line therapy in patients with metastatic colorectal cancer (JSWOG-C3 study).

BACKGROUND: Triweekly capecitabine plus irinotecan (CAPIRI) was not a replacement for fluorouracil, leucovorin, and irinotecan (FOLFIRI) in the treatment of metastatic colorectal cancer (mCRC) because of the potential for greater toxicity. Recently, it has reported that mCAPIRI is well tolerated and non-inferior to FOLFIRI. In this study, we conducted a multicenter phase II trial to assess the efficacy and safety of biweekly CAPIRI plus bevacizumab as second-line chemotherapy for mCRC with reduced toxicity and preserved efficacy. METHODS: Patients with mCRC who had received prior chemotherapy, including oxaliplatin-based regimens, were eligible for this study. The treatment protocol administered capecitabine at 1000 mg/m2 twice daily from the evening of day 1 to the morning of day 8, intravenous irinotecan at 150 mg/m2 on day 1, and bevacizumab at 10 mg/kg on day 1 every 2 weeks. Primary endpoints for this study were progression-free survival (PFS) and safety. Secondary endpoints were overall survival (OS), time to treatment failure, response rate (RR), and disease control rate (DCR). RESULTS: Fifty-one patients were enrolled in this study. Median PFS was 5.5 months [95% confidence interval (CI) 4.23-7.40 months], and median OS was 13.5 months (95% CI 11.57-20.23 months). The RR was 14.6% (95% CI 6.5-28.4%), and the DCR was 66.7% (95% CI 51.5-79.2%). Hypertension was the most common Grade 3 adverse event (27.5%), followed by neutropenia (17.6%). Only two patients suffered from grade 3 hand-foot syndrome. CONCLUSIONS: In mCRC patients, biweekly CAPIRI + bevacizumab appears effective and feasible as a second-line chemotherapy with relatively low toxicities, and has potential as a useful substitute for FOLFIRI + bevacizumab.

Treatment of Metastatic Biliary Cancers With Irinotecan and 5-Fluorouracil Based Chemotherapy After Platinum/Gemcitabine Progression: A Systematic Review and Meta-Analysis.

BACKGROUND: Biliary tract carcinomas are cancers that, despite a lower prevalence compared with other gastrointestinal cancers, represent a significant public health burden due to their aggressiveness. The metastatic stage of the disease is highly lethal and difficult to treat. Options of systemic therapies, especially beyond the first line are few and less well established. METHODS: We performed a systematic review of literature databases to identify studies of the combination of irinotecan and 5-fluorouracil (5-FU) based chemotherapy as treatment of metastatic biliary tract carcinomas in second line, after first line treatment with platinum/gemcitabine chemotherapy. Both prospective and retrospective designs were admissible. A meta-analysis of identified studies to determine summary estimates for overall response rate (ORR), disease control rate (DCR), progression free survival (PFS) and overall survival (OS) was also performed. RESULTS: The search was performed in PubMed/Medline and in Embase databases and identified a total of 339 articles. Manual review resulted in 8 articles that were eligible for inclusion in the meta-analysis. Second line irinotecan/5-FU based combinations produced an ORR of 9.1% (95% CI, 5.5%-12.6%) and DCR of 43.3% (95% CI, 15.8%-70.8%). Summary PFS and OS were 2.7 months (95% CI, 2.3-3.1 months) and 6.8 months (95% CI, 5.6-8.0 months), respectively. Treatments appeared to be feasible with adverse effect profiles as expected from the combination. CONCLUSION: A moderate activity of second line irinotecan/5-FU based chemotherapy was observed in this meta-analysis. The combination is an option for patients progressing on platinum/gemcitabine chemotherapy, who maintain a sufficient general status to receive active therapy. This combination may also serve as the control arm of second line trials with new targeted agents.

Capecitabine/irinotecan or capecitabine/oxaliplatin in combination with bevacizumab is effective and safe as first-line therapy for metastatic colorectal cancer: a randomized phase II study of the AIO colorectal study group.

BACKGROUND: This randomized phase II trial investigated the efficacy and safety of capecitabine/oxaliplatin (CapOx) plus bevacizumab and dose-modified capecitabine/irinotecan (mCapIri) plus bevacizumab as first-line therapy in patients with metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: Patients received bevacizumab 7.5 mg/kg with oxaliplatin 130 mg/m(2)/day 1 plus capecitabine 1000 mg/m(2) bid/days 1-14 or with irinotecan 200 mg/m(2)/day 1 plus capecitabine 800 mg/m(2) bid/days 1-14 both every 21 days. The primary end point was 6 months progression-free survival (PFS). RESULTS: A total of 255 patients were enrolled. The intent-to-treat population comprised 247 patients (CapOx-bevacizumab: n = 127; mCapIri-bevacizumab: n = 120). The six-month PFS rates were 76% (95% CI, 69%-84%) and 84% (95% CI, 77%-90%). Median PFS and OS were 10.4 months (95% CI, 9.0-12.0) and 24.4 months (95% CI, 19.3-30.7) with CapOx-bevacizumab, and 12.1 months (95% CI, 10.8-13.2) and 25.5 months (95% CI, 21.0-31.0) with mCapIri-bevacizumab. Grade 3/4 diarrhea as predominant toxic effect occurred in 22% of patients with CapOx-bevacizumab and in 16% with mCapIri-bevacizumab. CONCLUSIONS: Both, CapOx-bevacizumab and mCapIri-bevacizumab, show promising activity and an excellent toxic effect profile. Efficacy is in the range of other bevacizumab-containing combination regimen although lower doses of irinotecan and capecitabine were selected for mCapIri.

Second-Line Palliative Chemotherapy in Advanced Gall Bladder Cancer, CAP-IRI: Safe and Effective Option.

INTRODUCTION: Gall bladder cancer (GBC) has high prevalence in the Indo-Gangetic belt in India. While the first-line chemotherapy (CT1) has been established as gemcitabine-platinum doublet in advanced GBC, there is no standard recommendation or guidelines regarding feasibility of second-line therapy. METHODS: We performed a retrospective analysis of all patients who received second-line of chemotherapy (CT2) at our institution from July 2012 to December 2014. Patient records were examined for efficacy and toxicity of administered CT2, along with response rates (RR) and survival. Potential prognostic factors were also evaluated. RESULTS: Eighty-seven patients received CT2 in the predefined period. Ninety-nine percent of patients had received a gemcitabine-based regimen as CT1 with a median progression-free survival (PFS) of 5 months before CT2. 51.7 % patients had undergone surgery prior with 5.7 % patients having received radiotherapy previously. Prior to beginning CT2, PS was 0/1 in 67.8 % patients, albumin was >4 g% in 40.2 % and CA 19.9 was raised in a majority (66.7 %) patients, respectively. As per institution protocol, a majority of patients (89.6 %) were administered CAP-IRI regimen. Overall RR and disease control rates (DCR) were 21.8 % and 41.3 %, respectively. Median progression-free survival (PFS) and overall survival (OS) were 6 and 8 months, with no significant differences between CAP-IRI and other regimens. Adverse effects were tolerable, with dose reduced upfront in 23 % patients and 11.5 % patients during subsequent cycles of CT. ECOG Performance Status (PS) of 0/1 was a significant prognostic variable for OS on multivariate analysis (p = 0.003). CONCLUSION: CAP-IRI is a well-tolerated second-line chemotherapeutic regimen in patients with advanced GBC. Careful selection of patients is required when administering second-line chemotherapy to advanced GBC patients, with particular emphasis on ECOG PS.