Outcome of weekly carboplatin–paclitaxel-based definitive chemoradiation in oesophageal cancer in patients not considered to be suitable for platinum–fluoropyrimidine-based treatment: a multicentre, retrospective review

Owens, R., Cox, C., Gomberg, S., Pan, S., Radhakrishna, G., Parikh, S., Goody, R., Hingorani, M., Prince, S., Bird, T., Dorey, N., Macgregor, U., Al-Chamali, H., Hurt, C. and Mukherjee, S. (2019) Outcome of weekly carboplatin–paclitaxel-based definitive chemoradiation in oesophageal cancer in patients not considered to be suitable for platinum–fluoropyrimidine-based treatment: a multicentre, retrospective review. Clinical Oncology, 32 (2), 121-130. (doi:10.1016/j.clon.2019.09.058).

Abstract

Aims: although cisplatin–fluoropyrimidine-based definitive chemoradiotherapy (dCRT) is a standard of care for oesophageal cancer, toxicity is significant and limits its use in elderly and frail patients. Weekly carboplatin–paclitaxel-based dCRT provides a viable alternative, although prospective data are lacking in the dCRT setting. Here we report the results of a national, multicentre retrospective review of outcome in patients treated with weekly carboplatin–paclitaxel-based dCRT.

Materials and methods: in this multicentre retrospective study of nine radiotherapy centres across the UK we evaluated the outcome of patients who had non-metastatic, histologically confirmed carcinoma of the oesophagus (adenocarcinoma, squamous cell or undifferentiated; World Health Organization performance status 0–2; stage I–III disease) and had been selected to receive weekly carboplatin–paclitaxel-based dCRT as they were considered not suitable for cisplatin–fluoropyrimidine-based dCRT. dCRT consisted of carboplatin AUC 2 and paclitaxel 50 mg/m2 (days 1, 8, 15, 22, 29) and the recommended radiation dose was 50 Gy in 25 daily fractions. We assessed overall survival, progression-free survival (PFS; overall, local and distant), proportion of patients who were failure free at the response assessment (12 weeks after dCRT), treatment compliance and toxicity.

Results: in total, 214 patients from nine UK centres were treated between 15 February 2013 and 19 March 2019: 39.7% of patients were ≥75 years; 18.7% ≥ 80 years. Indications for weekly carboplatin–paclitaxel-based dCRT were comorbidities (47.2%), clinician choice (36.4%) and poor tolerance/progression on cisplatin–fluoropyrimidine induction chemotherapy (15.8%). The median overall survival was 24.28 months (95% confidence interval 20.07–30.09) and the median PFS was 16.33 months (95% confidence interval 14.29–20.96). Following treatment, 69.1% (96/139) had a combined complete response on endoscopy with non-progression (complete response/partial response/stable disease) on imaging. The 1- and 2-year overall survival rates for this patient group were 81.9% (95% confidence interval 75.6–86.8%) and 50.6% (95% confidence interval 40.5–60.0%), respectively. Thirty-three per cent (n = 70) of patients experienced at least one grade 3 + acute toxicity (grade 3/4 haematological: 10%; grade 3/4 non-haematological: 32%) and there were no treatment-related deaths. 86.9% of patients completed at least four cycles of concomitant weekly carboplatin–paclitaxel-based chemotherapy and planned radiotherapy was completed in 97.7% (209/214).

Conclusion: weekly carboplatin–paclitaxel-based CRT seems to be well tolerated in elderly patients and in those with comorbidities, where cisplatin–fluoropyrimidine-based dCRT is contraindicated. Survival outcomes are comparable with cisplatin–fluoropyrimidine-based dCRT.

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Contributors

Author: C. Hurt

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