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Critical role of bevacizumab scheduling in combination with pre-surgical chemo-radiotherapy in MRI-defined high-risk locally advanced rectal cancer: Results of the BRANCH trial.
- Source :
-
Oncotarget [Oncotarget] 2015 Oct 06; Vol. 6 (30), pp. 30394-407. - Publication Year :
- 2015
-
Abstract
- Background: We have previously shown that an intensified preoperative regimen including oxaliplatin plus raltitrexed and 5-fluorouracil/folinic acid (OXATOM/FUFA) during preoperative pelvic radiotherapy produced promising results in locally advanced rectal cancer (LARC). Preclinical evidence suggests that the scheduling of bevacizumab may be crucial to optimize its combination with chemo-radiotherapy.<br />Patients and Methods: This non-randomized, non-comparative, phase II study was conducted in MRI-defined high-risk LARC. Patients received three biweekly cycles of OXATOM/FUFA during RT. Bevacizumab was given 2 weeks before the start of chemo-radiotherapy, and on the same day of chemotherapy for 3 cycles (concomitant-schedule A) or 4 days prior to the first and second cycle of chemotherapy (sequential-schedule B). Primary end point was pathological complete tumor regression (TRG1) rate.<br />Results: The accrual for the concomitant-schedule was early terminated because the number of TRG1 (2 out of 16 patients) was statistically inconsistent with the hypothesis of activity (30%) to be tested. Conversely, the endpoint was reached with the sequential-schedule and the final TRG1 rate among 46 enrolled patients was 50% (95% CI 35%-65%). Neutropenia was the most common grade ≥ 3 toxicity with both schedules, but it was less pronounced with the sequential than concomitant-schedule (30% vs. 44%). Postoperative complications occurred in 8/15 (53%) and 13/46 (28%) patients in schedule A and B, respectively. At 5 year follow-up the probability of PFS and OS was 80% (95%CI, 66%-89%) and 85% (95%CI, 69%-93%), respectively, for the sequential-schedule.<br />Conclusions: These results highlights the relevance of bevacizumab scheduling to optimize its combination with preoperative chemo-radiotherapy in the management of LARC.
- Subjects :
- Adult
Aged
Angiogenesis Inhibitors adverse effects
Antineoplastic Combined Chemotherapy Protocols adverse effects
Bevacizumab adverse effects
Disease Progression
Disease-Free Survival
Drug Administration Schedule
Early Termination of Clinical Trials
Female
Fluorouracil administration & dosage
Humans
Italy
Kaplan-Meier Estimate
Leucovorin administration & dosage
Male
Middle Aged
Neoplasm Recurrence, Local
Organoplatinum Compounds administration & dosage
Oxaliplatin
Predictive Value of Tests
Quinazolines administration & dosage
Rectal Neoplasms mortality
Rectal Neoplasms pathology
Risk Factors
Thiophenes administration & dosage
Time Factors
Treatment Outcome
Angiogenesis Inhibitors administration & dosage
Antineoplastic Combined Chemotherapy Protocols therapeutic use
Bevacizumab administration & dosage
Chemoradiotherapy, Adjuvant adverse effects
Chemoradiotherapy, Adjuvant mortality
Magnetic Resonance Imaging
Neoadjuvant Therapy adverse effects
Neoadjuvant Therapy mortality
Rectal Neoplasms therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1949-2553
- Volume :
- 6
- Issue :
- 30
- Database :
- MEDLINE
- Journal :
- Oncotarget
- Publication Type :
- Academic Journal
- Accession number :
- 26320185
- Full Text :
- https://doi.org/10.18632/oncotarget.4724