Phase II study of bevacizumab and cetuximab as neoadjuvant treatment in locally advanced rectal cancer: A preliminary security report.

Abstract

627 Background: Concurrent chemoradiotherapy is the standard treatment in locally advanced rectal cancer. Bevacizumab and cetuximab are accepted today in the treatment of metastatic colorrectal cancer. We evaluate the activity and security of these drugs in the neoadyuvante setting. Methods: Ten patients have been included so far. Treatment consists in a first phase with induction treatment with capecitabine 2,000 mg/m2 D1-14, oxaliplatin 130 mg/m2 and bevacizumab 7.5 mg/kg every 3 weeks for two cycles. In sequential form a second phase that consist in external beam radiation therapy that was given at 50.4 Gy in 28 sesions concurrently with capecitabine 1,300 mg/m2 /d continuous during radiotherapy with cetuximab 400 mg/m2 every two weeks in patients with k-ras wild type. Results: 10 patients completed induction treatment and eight patients completed the concurrent phase. As of today, two patients are still on treatment. At this point, four patients have been operated; three patients are still waiting for surgery, and one avoided surgery. During induction treatment the main toxicity was disesthesias in eight patients, four patient presented grade 2 emesis, two presented grade 2 altered liver function test, two had grade 2 hand foot syndrome. One patient presented grade 3 hemorrhage. During the second phase, eight patients received cetuximab and presented rash grade 1-2, diarrhea grade 1 in five patients, emesis grade 1 in four patients, anemia grade 2 in two patients, proctitis grade 2 in four patients, and grade 3 in one patient. From four patients who were operated two presented complete pathological response and two have tumor persistence. Conclusions: The combination of chemoradiation with bevacizumab and cetuximab seems to be secure with no increment in toxicity and those presented are acceptable and manageable. No significant financial relationships to disclose.

Neoadjuvant therapy before surgical treatment

“…Clinical response rates with induction chemotherapy vary between 28% [120], 41% [27] and 59% [119] when cetuximab was added, with no patients observed to have progressive disease.…”

“…including cCR and pCR) of 65% [27]. Recent studies have tested the hypothesis that by delaying surgery or increasing the interval between CRT and surgery, and allowing more time for response or even administration of two additional cycles of FOLFOX chemotherapy, it may be feasible to increase down-staging and achieve a higher rate of pCR [29,122].…”

“…Yet the risk of dying from rectal cancer is linked mainly to the development of distant metastases, and to experience a late local recurrence as described by Sauer et al [23] the patient needs to survive 5 years. As an alternative setting to concurrent chemoradiation (which only delivers 5–6 weeks of chemotherapy), potential options are an induction component of 6–12 weeks of neoadjuvant chemotherapy (NACT) prior to radiotherapy or chemoradiation [20,24–27] , adding chemotherapy after SCPRT or chemoradiation (defined as consolidation chemotherapy) which utilises the “dead space” of the interval between the end of chemoradiation and surgery [28–30] , or delivering chemotherapy alone without any radiotherapy [31,32] .…”

“…The most popular method of integrating chemotherapy is as induction prior to chemoradiation, which achieves high rates of symptomatic improvement (65%) [120] . Clinical response rates with induction chemotherapy vary between 28% [120] , 41% [27] and 59% [119] when cetuximab was added, with no patients observed to have progressive disease.…”

The contribution of targeted therapy to the neoadjuvant chemoradiation of rectal cancer

“…Preliminary results of a phase II trial have been recently presented [60]. Ten patients with K-RAS wild type tumor received an induction treatment with capecitabine (2000 mg/m 2 day 1-14), oxaliplatin (130 mg/m 2 ) and bevacizumab (7.5 mg/kg) every 3 weeks for two cycles followed by capecitabine (1300 mg/m 2 /day) continuously during radiotherapy and cetuximab 400 mg/m 2 every two weeks.…”