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Michael Xiang and Elizabeth A. Kidd

Background: Cisplatin with definitive radiotherapy (RT) is considered the standard of care for cervical cancer; however, older women are frequently undertreated and have worse outcomes compared with younger patients. Because women aged ≥65 years have been disproportionately underrepresented in clinical trials, uncertainties exist regarding how much they benefit from the addition of cisplatin to RT. Patients and Methods: Women aged ≥65 years with nonmetastatic cervical cancer treated with definitive external-beam RT and brachytherapy were identified in the SEER-Medicare database. Death attributable to cervical cancer (cancer-specific mortality [CSM]) was evaluated against competing risks of death using Gray’s test. Propensity score analysis and the Fine-Gray multivariable regression model were used to adjust for baseline differences, including comorbidity. Results: The total cohort comprised 826 patients, of whom 531 (64%) received cisplatin, 233 (28%) were FIGO stage I, 374 (45%) were stage II, and 219 (27%) were stage III–IVA. Older age and chronic kidney disease significantly predicted omission of cisplatin. Virtually all cisplatin dosing was weekly, with a median of 5 cycles. Death from cervical cancer was significantly lower with cisplatin than without (5-year CSM, 31% vs 39%; P=.02; adjusted hazard ratio, 0.72; P=.02), which persisted in propensity score analysis. Receiving ≥5 cycles was required for benefit, as no difference in CSM was seen in patients receiving 1 to 4 cycles versus no cisplatin. Subgroup analyses revealed that the benefit of cisplatin persisted in women aged ≥75 years and those with early-stage disease. Incidence of cytopenia, nausea/vomiting, and hypovolemia increased in patients treated with cisplatin. Conclusions: Administration of cisplatin with definitive RT in women aged ≥65 years was associated with a significant benefit in the incidence of death attributable to cervical cancer, despite competing risks for mortality in an older population. Receiving at least 5 cycles of weekly cisplatin was required for benefit.

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Michael Xiang, A. Dimitrios Colevas, F. Christopher Holsinger, Quynh-Thu X. Le and Beth M. Beadle

Background: For definitive chemoradiotherapy (chemoRT) of head and neck squamous cell carcinoma (HNSCC), cisplatin is the preferred concurrent agent, with superiority over cetuximab for HPV-associated oropharyngeal squamous carcinoma recently shown in 2 randomized trials (RTOG 1016 and De-ESCALaTE). Patients who are not candidates for cisplatin may be treated with carboplatin instead, but its comparative efficacy is unclear. We analyzed nationwide patterns of care and cancer-specific outcomes after cisplatin- versus carboplatin-based chemoRT. Patients and Methods: Patients with locoregionally advanced (stages III–IVB according to the 6th and 7th editions of the AJCC Cancer Staging Manual) squamous cell carcinoma of the oropharynx, larynx, or hypopharynx who received definitive radiotherapy (RT) were identified in the linked SEER-Medicare database. The concurrent chemotherapy regimen was determined through corresponding Medicare claims. Death caused by HNSCC (cancer-specific mortality [CSM]) was analyzed with competing risks. Propensity score analysis and multivariable Fine-Gray regression were used to adjust for baseline differences, including age and comorbidity. Results: We identified 807 patients who received cisplatin-based chemoRT and 342 who received carboplatin-based chemoRT. Most carboplatin recipients (68%) had combination chemotherapy, predominantly with paclitaxel. Carboplatin- and cisplatin-based chemoRT had similar incidences of death attributable to HNSCC (3-year CSM, 29% vs 26%; P=.19), which persisted in propensity score–matched analysis. In addition, no significant difference in overall survival was seen in the matched cohorts. ChemoRT with either cisplatin or carboplatin was superior to RT alone and RT with concurrent cetuximab. In the multivariable model, the adjusted hazard ratio of CSM for carboplatin relative to cisplatin was 1.01 (95% CI, 0.79–1.28; P=.94). Conclusions: Definitive carboplatin-based chemoRT was equivalent to cisplatin-based therapy and superior to RT alone and RT with concurrent cetuximab. In light of recent results of the RTOG 1016 and De-ESCALaTE trials, our findings suggest that carboplatin-based regimens warrant prospective investigation as an alternative to cisplatin for patients who are not cisplatin candidates.