CHOP療程為基礎的化學治療在犬多中心型淋巴瘤的毒性反應以及腫瘤治療效果間的相關性

Abstract

本研究目的為探討犬多中心型淋巴瘤的化療毒性以及療效間的相關性。六十九隻罹患多中心型淋巴瘤且在國立台灣大學附設動物醫院接受以CHOP療程為基礎的化學治療的犬隻的病歷被回顧，並且分析其中骨髓毒性以及消化道毒性對於疾病進展時間(Time to tumor progression, TTP)，總存活時間(Overall survival time, OST)，以及短期的腫瘤抑制效果的影響。嗜中性球低點小於5000/μl可增進OST (P =0.045)。出現食慾不振、嘔吐、腹瀉其中一種消化道毒性或者僅出現嘔吐皆可增加TTP 及OST (P =0.042, 0.007對於TTP; 0.023, <0.001對於OST)。出現毒性分級三或四的腹瀉會降低TTP及OST (P =0.034, 0.017)。年齡超過十歲較不容易出現毒性分級低的消化道毒性，同時也有較不理想的治療成果。在單次治療後出現嗜中性球低下或者消化道毒性，會增加該次治療成為有效治療而非無效治療的可能性，顯示毒性以及短期療效之間存在正向關係。本研究的結果支持依據毒性反應來調整藥物劑量的概念，但是必須靠前瞻性研究才能建立起完善的依據毒性做劑量調整的規範。

This study was aimed at investigating the correlation between chemotherapy toxicity and antitumor efficacy in canine multicentric lymphoma. Medical records of 69 dogs with multicentric lymphoma received CHOP-based chemotherapy at National Taiwan University Veterinary Hospital were reviewed, and impact of bone marrow toxicity and GI toxicity on time to tumor progression (TTP), overall survival time (OST), and short-term tumor-killing effect was evaluated. Neutrophil nadir lower than 5000 /μl improved OST (P =0.045). Presence of GI signs, including anorexia, vomiting, and diarrhea, or presence of only vomiting improved TTP and OST (P =0.042, 0.007 for TTP; 0.023, <0.001 for OST). Presence of diarrhea of grade 3 or 4 decreased TTP and OST (P =0.034, 0.017). More than 10 years old was associated with less low-grade GI toxicities and less favorable outcome. Occurrence of neutropenia or GI toxicity after a treatment increased the like hood of effective treatment over ineffective treatment, implying a positive relationship between toxicity and short-term efficacy. The results of the study supported the concept of toxicity-adjusted dosing, but prospective trials are warranted to develop a sophisticated toxicity-adjusted dosing regimen.