Efficacy of oral administration of cystine and theanine in colorectal cancer patients undergoing capecitabine-based adjuvant chemotherapy after surgery: a multi-institutional, randomized, double-blinded, placebo-controlled, phase II trial (JORTC-CAM03)

• Published in: Supportive care in cancer Vol. 28; no. 8; pp. 3649 - 3657
• Main Authors: Hamaguchi, Reo, Tsuchiya, Takashi, Miyata, Go, Sato, Toshihiko, Takahashi, Kenichi, Miura, Koh, Oshio, Hiroshi, Ohori, Hisatsugu, Ariyoshi, Keisuke, Oyamada, Shunsuke, Iwase, Satoru
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-08-2020; Springer; Springer Nature B.V
• Subjects: Adjuvant treatment; Administration, Oral; Adult; Aged; Aged, 80 and over; Amino acids; Anorexia - chemically induced; Anorexia - drug therapy; Antimitotic agents; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Cancer; Cancer patients; Cancer surgery; Capecitabine - administration & dosage; Capecitabine - adverse effects; Chemotherapy; Chemotherapy, Adjuvant; Clinical trials; Colorectal cancer; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - surgery; Complications and side effects; Cystine - adverse effects; Cystine - therapeutic use; Diarrhea; Diarrhea - chemically induced; Diarrhea - drug therapy; Double-Blind Method; Drug therapy; Drug-Related Side Effects and Adverse Reactions - drug therapy; Female; Glutamates - adverse effects; Glutamates - therapeutic use; Hand-Foot Syndrome - drug therapy; Hand-Foot Syndrome - etiology; Humans; Male; Medical colleges; Medicine; Medicine & Public Health; Middle Aged; Nursing; Nursing Research; Oncology; Original; Original Article; Pain Medicine; Product development; Rehabilitation Medicine; Side effects; Stomatitis - chemically induced; Stomatitis - drug therapy; Diarrhea; Cystine and theanine; Adverse events; Capecitabine; Colorectal cancer; Hand-foot syndrome
• ISSN: 0941-4355; 1433-7339
• DOI: 10.1007/s00520-019-05205-1

Purpose
Capecitabine-based adjuvant chemotherapy for colorectal cancer patients often causes adverse events (AEs), such as diarrhea, stomatitis, anorexia, and hand-foot syndrome (HFS). Cystine and theanine were reported to attenuate some chemotherapy-associated AEs, and hence are also expected to attenuate capecitabine-induced AEs. Therefore, we aimed to investigate the safety and efficacy of cystine/theanine treatment in colorectal cancer patients undergoing capecitabine-based adjuvant chemotherapy after surgery.
Methods
A total of 100 colorectal cancer patients treated with capecitabine as an adjuvant chemotherapy after surgery were randomly allocated into the cystine/theanine group (
n
= 52) or the placebo group (
n
= 48). The primary endpoint was incidence rate of diarrhea of grade 1 or higher in accordance with the Common Terminology Criteria for AEs (CTCAE) v.4.0, Japanese Clinical Oncology Group (JCOG) version. The secondary endpoints included incidence rates of other AEs (CTCAE v.4.0-JCOG), as well as the incidence rate of HFS according to the HFS grading scale.
Results
There were no significant differences in capecitabine-induced AEs between the two groups. However, the incidence rate of diarrhea of grade 1 or higher tended to be lower in the cystine/theanine group than the placebo group (18.4% vs. 28.9%,
p
= 0.169) as well as the incidence rate of HFS of grade 1 or higher (CTCAE v.4.0-JCOG or HFS grading scale) (67.4% vs. 77.8%,
p
= 0.185, 67.3% vs. 80.0%,
p
= 0.124, respectively).
Conclusion
This trial demonstrated that cystine/theanine treatment of colorectal cancer patients undergoing capecitabine-based adjuvant chemotherapy after surgery is safe and has the tendency to reduce the incidence rate of diarrhea or HFS.
Trial registration
UMIN000024784