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FU/mitomycin yielded positive long-term outcomes in anal carcinoma
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Five-year follow-up data from a previous study indicated that radiation therapy plus fluorouracil/mitomycin yielded statistically better survival outcomes than radiation plus fluorouracil/cisplatin in a cohort of patients with anal carcinoma.
Leonard L. Gunderson
Leonard L. Gunderson, MD, MS, emeritus professor and consultant in the department of radiation oncology at Mayo Clinic in Scottsdale, Ariz., and colleagues conducted the study as an update to the GI Intergroup Radiation Therapy Oncology Group 98-11 phase 3 trial, which involved patients with anal carcinoma.
“Patients with anal canal cancer treated with the widely accepted standard therapy of irradiation plus concurrent fluorouracil (5-FU) and mitomycin live significantly longer than those treated with an experimental regimen of induction 5-FU plus cisplatin followed by RT plus concurrent 5-FU and [cisplatin],” Gunderson told HemOnc Today.
The results of the original study indicated that concurrent chemoradiation with fluorouracil (FU) plus mitomycin was associated with decreases in colostomy failure when compared with induction plus concurrent FU plus cisplatin, but did not significantly affect DFS or OS.
The researchers performed the update to evaluate long-term DFS, OS, colostomy-free survival and relapse, which included locoregional failure and distant metastasis.
Patients were stratified by sex, clinical node status and primary size.
The final analysis included 649 of the 682 patients accrued.
The 5-year DFS was 67.8% in the FU/mitomycin group vs. 57.8% in the FU/cisplatin group, which the researchers said was statistically better (P=.006). OS outcomes at 5 years also were statistically better in the FU/mitomycin group (78.3% vs. 70.7%; P=.026).
The researchers observed a trend toward statistical significance for colostomy-free survival (P=.05), locoregional failure (P=.087) and colostomy failure (P=.074).
“Multivariate analysis was statistically significant for treatment and clinical node status for both DFS and OS, for tumor diameter for DFS, and for sex for OS,” the researchers wrote.
“From our perspective, there is no role for induction chemotherapy prior to concurrent chemoradiation based on both the current US GI Intergroup RTOG 98-11 trial and a separate ACCORD 03 trial,” Gunderson said. “With regard to whether 5FU/[cisplatin] is appropriate as concurrent chemotherapy during irradiation, the results of RTOG 98-11 suggest that concurrent 5FU/[cisplatin] should be considered primarily when mitomycin is contraindicated (ie, a significant blood disorder or allergy from prior exposure).”
Radiation plus FU/mitomycin remains the standard of care in this patient population, the researchers concluded.
“With regard to potential new treatment strategies, treatment intensification, treatment modification based on PET/CT response and individualized molecular-based treatment with targeted agents may play a role in future investigations,” Gunderson said. “Intensity-modulated irradiation approaches are being evaluated to minimize treatment related morbidity and allow the possibility of increased irradiation dose and shortened treatment times.”
Reference:
Gunderson LL. J Clin Oncol. 2012;doi:10.1200/JCO.2012.43.8085.
For more information:
Leonard L. Gunderson, MD, MS, may be reached at Mayo Clinic Scottsdale, Radiation Oncology, 13400 E. Shea Blvd., Scottsdale, AZ 85259.
Disclosure: Gunderson reports no relevant financial disclosures.
Perspective
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May Abdel-Wahab, MD
The Intergroup trial (RTOG 98-11) is a well-designed, landmark phase 3 randomized study of patients with anal canal carcinoma. The trial compared a standard arm — concurrent chemoradiation (CCR) with 5-FU, Mitomycin (5-FU/MMC) — to an experimental arm, in which patients underwent induction chemotherapy and concurrent chemoradiation with 5-FU, Cisplatin (5-FU/CDDP.
The initial report only showed that the standard arm (5-FU/MMC) significantly decreased colostomy failure (CF) while the updated analysis showed that the standard arm (5-FU/MMC) had a statistically significant improvement in 5-year DFS (67.8% vs. 57.8%; P=.006) and OS (78.3% vs. 70.7%; P=.026). Treatment arm and clinical lymph node status significantly predicted DFS and OS on multivariate analysis. Tumor diameter was significant for DFS. OS was significantly influenced by gender, with males having a higher risk of death.
It is important to note that this study should not be interpreted as a comparison between two types of chemotherapy (ie, RT plus FU/MMC vs. RT plus FU/CDDP) since the induction chemotherapy in the experimental arm (RT plus FU/CDDP) complicates the interpretation. This study does confirm, however, that RT plus FU/MMC should remain the standard of care rather than induction chemotherapy followed by RT plus FU/CDDP.
The other issues that must be noted is the lack of HIV screening in these patients, and only patients with AIDS were excluded. Depending on the distribution of patients, this may have had an impact on survival outcomes in the study arms — especially before widespread availability of highly active antiretroviral therapy. In addition, the unequal burden in the early days of the HIV epidemic on the male demographic may have contributed to the decrease in OVS in unscreened males. The use of older radiation techniques also may be an additional factor that affected the results, since newer intensity-modulated radiation methods have been shown to decrease toxicity. Nevertheless, this well-designed, well-executed study continues to provide important information as to the effectiveness of the RT plus FU/MMC. Further stratification by biologic predictors of response and use of newer drugs (eg, capecitabine) may lead to more convenient, simpler and more effective treatment methods.
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