Usefulness of an S-1 dosage formula for predicting adverse events in adjuvant chemotherapy for curatively resected pancreatic cancer: an exploratory analysis of the randomized clinical trial (JASPAC-01).

BACKGROUND

Adverse events (AEs) of S-1 are affected by renal function. A dosage formula for S-1 based on renal function and body surface area (BSA) has been developed, indicating the dose required to achieve a target blood concentration of 5-fluorouracil. This study aimed to explore the usefulness of this formula in adjuvant chemotherapy with S-1 for pancreatic cancer (PC).

METHODS

In the JASPAC-01 trial, the actual initial dose of S-1 was calculated based on the BSA. Patients were divided into three groups by comparing the actual initial S-1 dose with the dose recommended by the S-1 dosage formula: underdose (UD), equal dose (ED), and overdose (OD). The recurrence rate, prognosis, and AEs in each group were evaluated.

RESULTS

Among 187 eligible patients, 27 (14%), 43 (23%), and 117 (63%) patients were classified into the UD, ED, and OD groups. The incidence of all-grade and grade ≥ 3 anemia during the all-time periods were significantly higher in the OD group (94.9/18.8%) compared to the ED (93.0/4.7%) and UD (81.5/7.4%) groups (P = 0.04). In the UD/ED/OD groups, the planned adjuvant S-1 therapy for 6 months was completed in 77.8/72.1/70.9% (P = 0.51), whereas dose reduction was required in 0/14.0/22.2% (P = 0.01). The 5-year overall survival was slightly worse in OD group (41.9%) than those in the UD/ED groups (48.1/47.6%).

CONCLUSIONS

In the adjuvant S-1 therapy for PC, AEs and dose reduction were more common in the OD group. The S-1 dosage formula may be useful for reducing AEs.