Induction-concurrent chemotherapy sequence shows promise in nasopharyngeal carcinoma
An induction-concurrent chemotherapy sequence conferred a PFS benefit for patients with locoregionally advanced nasopharyngeal carcinoma treated with conventional fractionated radiotherapy, according to study results published in Cancer.
Researchers also observed marginal improvement in OS with a favorable toxicity profile.
“A current recommendation for the treatment of patients with locoregionally advanced nasopharyngeal carcinoma is conventional fractionated radiotherapy with concurrent cisplatin followed by adjuvant cisplatin and 5-fluorouracil,” Anne W.M. Lee, MD, clinical professor and head of the department of clinical oncology at The University of Hong Kong, and colleagues wrote. “This randomized NPC-0501 trial evaluated the therapeutic effect of changing to an induction-concurrent sequence or accelerated fractionation sequence and/or replacing 5-fluorouracil with capecitabine.”
Between 2006 and 2012, researchers accrued 802 patients with stage III to stage IVB nasopharyngeal carcinoma. The investigators initially assigned patients to one of six treatment arms. To improve accrual, the protocol was amended in 2009 to allow individual centers that encountered logistical difficulties in arranging six fractions per week to opt out of the accelerated-fractionation portion of the trial. This resulted in 578 patients in the six-arm, full-randomization cohort and 224 patients in a three-arm chemotherapy cohort. Researchers amended the protocol further in 2011 to include comparison of chemotherapy sequence as a secondary objective.
At a median follow-up of 8.4 years, researchers found that neither changing the chemotherapy sequence nor accelerated fractionation improved outcomes.
Results of secondary analyses of treatment factors showed a significant imbalance regarding radiotherapy dose and/or fraction and total dose (P < .001 for both). Researchers observed marked heterogeneity in radiotherapy prescription schedules, with dose per fraction ranging from 1.8 Gy to 2.27 Gy and total dose ranging from 66 Gy to 74 Gy.
When researchers compared the induction-concurrent vs. concurrent-adjuvant chemotherapy sequence among patients assigned conventional fractionation, they observed a significant 5-year PFS benefit (78% vs. 62%; P = .015). After adjusting for multiple comparisons, researchers additionally observed a marginal benefit in OS (84% vs. 72%; P = .042).
“To our knowledge, the current trial is the first to indicate that acceleration could negate the potential benefit of changing from a concurrent-adjuvant sequence to an induction-concurrent sequence,” Lee and colleagues wrote. “Hence, we concur with the National Comprehensive Cancer Network guideline that treatment with 70 Gy to 70.2 Gy, at 1.8 Gy to 2 Gy per fraction, for five fractions per week is the preferred concurrent radiotherapy regimen.”
The trial conducted by Lee and colleagues is ambitious and complex, according to an editorial accompanying the study by Stefano Cavalieri, MD, and Lisa Licitra, MD, oncologists in the head and neck medical oncology unit at Fondazione IRCCS Istituto Nazionale dei Tumori in Milan.
“One could speculate that the observed benefit of induction might be due to the salvage role of adding further chemotherapy to a slight underdosing of radiotherapy rather than a lack of benefit from accelerated fractionation in itself,” they wrote. “Interestingly, a similar salvage effect was not seen when adjuvant chemotherapy was delivered. We cannot exclude that this happened because of different planned and delivered doses of chemotherapy in the treatment arms. We appreciate that the investigators are planning to conduct an additional exploratory analysis of actual treatment to elucidate what has been previously discussed.”
In another accompanying editorial, Nancy Y. Lee, MD, and Eric J. Sherman, MD, both of the department of radiation oncology at Memorial Sloan Kettering Cancer Center, wrote that because adjuvant chemotherapy and induction chemotherapy improve survival for patients with nasopharyngeal carcinoma who receive concurrent chemoradiation, the question remains: Which approach is superior?
“To definitively answer this eternally unfinished chemotherapy sequence question for nasopharyngeal carcinoma, a head-to-head comparison of induction chemotherapy followed by concurrent chemoradiation vs. adjuvant chemotherapy is needed,” they wrote. “This is a critical question to answer because there is always the concern that the definitive portion of nasopharyngeal carcinoma treatment — chemoradiation — can be compromised as a result of toxicities due to induction chemotherapy.”
References
- Cavalieri S and Licitra L. Cancer. 2020;doi:10.1002/cncr.32971.
- Lee AWM, et al. Cancer. 2020;doi:10.1002/cncr.32972.
- Lee NY and Sherman EJ. Cancer. 2020;doi:10.1002/cncr.32970.
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