Efficacy and tolerability of controlled-release oxycodone for oxaliplatin-induced peripheral neuropathy and the extension of FOLFOX therapy in advanced colorectal cancer patients.
BACKGROUND
The oxaliplatin-based regimen FOLFOX is widely used to treat patients with advanced colorectal cancer (CRC). However, dose-limiting toxicity after continuous oxaliplatin administration can lead to peripheral neuropathy. Several agents, including opioids, that have been employed to treat oxaliplatin-induced peripheral neuropathy (OIPN) have been examined in clinical settings regarding their protective and therapeutic effects. However, the pharmacotherapy of these agents has not yet been established. Therefore, we investigated the efficacy and tolerability of oxycodone for OIPN and subsequently with FOLFOX therapy in CRC patients.


METHODS
This was a single-center retrospective study of 64 CRC patients who underwent FOLFOX therapy at the Toho University Sakura Medical Center (Sakura, Japan). Controlled-release (CR) oxycodone was concomitantly administered to 29 patients (OXY group), whereas the additional 35 patients (non-OXY group) were not given oxycodone during the FOLFOX treatment course. The incidence and severity of OIPN and the number of FOLFOX cycles were measured and compared between the two groups. Neurological toxicities were assessed according to the Common Terminology Criteria for Advanced Events, version 3.0.


RESULTS
All study patients had OIPN. Most patients experienced grade 1 or 2 sensory neuropathy. Grade 3 sensory neuropathy was observed in two patients in the non-OXY group. All patients in the OXY group completed the scheduled FOLFOX therapy, whereas FOLFOX therapy was discontinued in ten patients in the non-OXY group due to severe peripheral neuropathy. The median numbers of FOLFOX cycles in the OXY and non-OXY groups were 13 (range, 6-46) and 7 (range, 2-18), respectively (P < 0.05). The median cumulative oxaliplatin doses were 1072.3 mg/m(2) (range, 408.7-3385.3 mg/m(2)) in the OXY group and 483.0 mg/m(2) (range 76.2-1414.1 mg/m(2)) in the non-OXY group (P < 0.05).


CONCLUSIONS
Our findings indicate that CR oxycodone might attenuate the severity of OIPN and extend the use of FOLFOX therapy.
Department of Surgery, Toho University Sakura Medical Center, 564-1 Shimoshizu, Sakura, 285-8741, Japan, nagashima@sakura.med.toho-u.ac.jp.
Makoto
M
Nagashima
Mitsuru
M
Ooshiro
Ayako
A
Moriyama
Yui
Y
Sugishita
Kengo
K
Kadoya
Ayami
A
Sato
Tomoaki
T
Kitahara
Ryuichi
R
Takagi
Tasuku
T
Urita
Yutaka
Y
Yoshida
Hiroshi
H
Tanaka
Takashi
T
Oshiro
Shinichi
S
Okazumi
Ryoji
R
Katoh
D000368:Aged; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D003692:Delayed-Action Preparations; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077150:Oxaliplatin; D010098:Oxycodone / Q000008:administration & dosage* / Q000009:adverse effects; D010146:Pain / Q000188:drug therapy / Q000209:etiology; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000188:drug therapy*; D012189:Retrospective Studies
D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D010098:Oxycodone; D002955:Leucovorin; D005472:Fluorouracil