The safety and short-term efficacy of neoadjuvant chemotherapy in elderly patients with resectable locally advanced esophageal squamous cell carcinoma.
Authors: Imazeki Hiroshi , Shiraishi Kazuhiro , Yamamoto Shun , Yokoyama Kazuki , Honma Yoshitaka , Kurita Daisuke , Ishiyama Koshiro , Oguma Junya , Daiko Hiroyuki , Seto Yasuyuki , Kato Ken 
Published: January 2025

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Background:
The standard treatment for resectable locally advanced esophageal squamous cell carcinoma (LA-ESCC) is neoadjuvant chemotherapy followed by surgery. However, the efficacy and safety of neoadjuvant chemotherapy for patients aged 76 or older have not been established because the JCOG1109 trial, which established the current standard of care, was limited to patients younger than 76 years. In our hospital, even patients aged 76 or older are treated with docetaxel, cisplatin, and 5-FU (DCF) or 5-FU / leucovorin, oxaliplatin, and docetaxel (FLOT), if the patient's general condition and organ function are maintained, but there have been few reports on the efficacy and safety of these therapies for elderly population.
Methods:
The subjects were 76 years old or older resectable LA-ESCC patients diagnosed as cT1N1-3M0, cT2-3N0-3M0, and cT1-3N0-3M1 (UICC-TNM 8th), who received at least one cycle of neoadjuvant DCF or FLOT in our institution from 2014 to 2023. Adverse events (CTCAE ver. 5.0) and histopathological responses were evaluated.
Results:
Patients who received neoadjuvant DCF (D group) and FLOT (F group) were 19 and 25, respectively. Patients background in the D / F group was as follows; median age 76 / 78 (years), male 84% / 64%, PS1 37% / 64%, clinical, T3 74% / 84%, clinical N1 32% / 52%, N2 47% / 32%, clinical stage III 53% / 64%, stage IVB 21% / 28%. Of the 19 patients in the D Group, 17 completed 3 cycles of treatment (completion rate 89%), 18 underwent surgery, including 2 patients who discontinued during the treatment (1 with disease progression and 1 with adverse event), and 1 underwent CRT. Of the 25 patients in the F group, 16 completed 4 cycles of treatment (completion rate 64%), 22 underwent surgery, including 8 patients who discontinued during the treatment (1 with disease progression, 6 with adverse events, and 1 with other), 2 underwent CRT, and 1 was placed on best supportive care. In the D and F groups, hematological toxicities were more common in the F group, especially grade 3 or more neutropenia was 26% / 96%, but febrile neutropenia was similar at 5% and 12%, respectively. Nonhematological toxicities were more common in the F group for all grades (nausea 42% / 64%, anorexia 63% / 80%, and fatigue 52% / 88%, while grade 3 or more toxicity was not significantly different from the D group (nausea 0% / 4%, anorexia 0% / 4%, and fatigue 5% / 4%). In the 18 patients of the D group and 22 patients of the F group who underwent surgery, R0 resection was performed in 94% / 95%, and pathological complete response (pCR) was 11% / 23%, respectively.
Conclusions:
Neoadjuvant triplet chemotherapy was well tolerated and resulted in high R0 resection rates and pathological responses even in patients aged 76 or older. Further investigation with long-term follow up is warranted to elucidate the clinical benefit of neoadjuvant chemotherapy for elderly LA-ESCC patients.