Patients with surgically unresectable metastatic colon cancer and an asymptomatic intact primary tumor can be spared initial noncurative resection of their intact primary tumor, National Surgical Adjuvant Breast and Bowel Project (NSABP) C-10 trial investigators reported in the Journal of Clinical Oncology. All 86 enrolled patients received infusional fluorouracil, leucovorin, and oxaliplatin (modified FOLFOX6) combined with bevacizumab (Avastin). “Combining [modified FOLFOX6] with bevacizumab did not result in an unacceptable rate of obstruction, perforation, bleeding, or death related to [the intact primary tumor]. Survival was not compromised,” the investigators stated.
“The primary objective of this trial was to determine the rate of major morbidity resulting from the presence of the [intact primary tumor] in patients treated initially with FOLFOX plus bevacizumab,” the authors explained. Any event related to the intact primary tumor that led to surgery or death was considered a major morbidity. Specifically, the primary endpoint was defined as “colonic bleeding, perforation, bowel obstruction, or fistula formation requiring surgery or resulting in patient death.”
Results showed that 86% of patients did not develop symptoms from the intact primary tumor that required surgery or problems resulting in death. “Of the 10 surgeries performed for symptoms related to the [intact primary tumor], only four (4.7%) were urgent among all 86 patients, and only three patients (3.5%) required permanent ostomies,” the researchers reported. “There were two patient deaths in which the [intact primary tumor] was likely a contributing cause.”
Initial Treatment Controversial
The authors noted that the initial treatment approach is controversial for patients with unresectable metastatic disease and an asymptomatic intact primary tumor. While initial resection of the primary tumor has been advocated to prevent future complications of colonic obstruction, bleeding, or perforation, “the 30-day operative mortality of colon resection for patients with distant metastases is as high as 10%.”
Retrospective series have suggested that with current chemotherapy regimens, problems related to the intact primary tumor may occur in 10% to 20% of patients. FOLFOX combined with bevacizumab has demonstrated improved overall survival in patients with metastatic colorectal cancer, but use of “bevacizumab has previously raised concerns of increased risk of tumor perforation for patients with [an intact primary tumor],” the authors wrote.
In the current study, the cumulative incidence of major morbidity was 16.3% at 24 months. “Importantly, we identified perforation of the [intact primary tumor] as a relatively rare event that should dispel a widespread and persistent reluctance to use bevacizumab” in this setting, the researchers reported.
”We believe this approach of primary systemic treatment with expectant observation … should define a new standard of care,” the investigators concluded. ■
McCahill L, et al: J Clin Oncol August 6, 2012 (early release online).