How often is adjuvant FOLFOX (Adj FOLFOX) discontinued for toxicity among colon cancer patients in the routine care setting?
Dorothy RomanusMartin R. WeiserA. terVeerJ. M. SkibberJane WilsonAshwani RajputYu Jun WongAngela BensonJ. C. NilandDeborah Schrag
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9530 Background: Although 12 cycles of Adj FOLFOX are recommended for stage III and high risk stage II colon cancer, toxicity may preclude completion of treatment. We used the NCCN Colorectal Cancer Outcomes Database to identify how frequently Adj FOLFOX is discontinued prematurely for toxicity in a non-clinical trial population. Methods: Newly diagnosed stage II-III colon cancer pts treated with Adj FOLFOX at 7 NCI-designated comprehensive cancer centers between 9/05–12/07 were identified. We assessed completion of the prescribed adjuvant chemotherapy (AC) course, including Adj FOLFOX and 5FU-based adjuvant treatment alone subsequent to discontinuation of oxaliplatin (oxal). Dose limiting toxicity (DLT) of Adj FOLFOX was defined as premature discontinuation of Adj FOLFOX due to toxicity. We evaluated potential predictors of Adj FOLFOX DLT, including older age and history of diabetes in a multivariable logistic model controlling for stage and center. We measured the duration of Adj FOLFOX use in weeks, from first to last dose. Results: 293 pts began Adj FOLFOX. Pts who experienced DLT (40%) had a shorter duration of Adj FOLFOX and were less likely to complete AC, even after oxal was discontinued. The only significant predictor of experiencing a DLT was a history of diabetes. Conclusions: Our analysis of patients treated outside of a clinical trial demonstrated a notably high rate of discontinuation of Adj FOLFOX due to DLT, particularly in pts with diabetes. The results underscore the need for systematic assessment of toxicity especially among diabetics. [Table: see text] [Table: see text]Keywords:
FOLFOX
Discontinuation
FOLFOX-4 Combination Chemotherapy as a First-line Treatment in Patients with Advanced Gastric Cancer
목ì : ì ì´ì± ìì íìë¤ìì 1ì°¨ ì¹ë£ë¡ì í¬ì¬ë oxaliplatin, 5-FU, leucovorin (FOLFOX-4) ë³í©ííìë²ì í¨ê³¼ì ìì ì±ì ëíì¬ ë¶ìíìë¤. ë°©ë²: 2006ë 8ìë¶í° 2009ë 2ìê¹ì§ ì¡°ì§íì ì¼ë¡ íì§íê³ ì ì ê° ë¶ê°ë¥í ì§í, ì ì´ì± ìì íì 35ëª ì ëìì¼ë¡ ì무기ë¡ì íµíì¬ íí¥ì ì¼ë¡ ì¡°ì¬íìë¤. Oxaliplatin 85 mg/m2ê³¼ leucovorin 200 mg/m2ì ì 1ì¼ì 2ìê° ëì ì 주íìì¼ë©°, 5-FUë 400 mg/m2ì bolusë¡, 600 mg/m2ì 22ìê° ëì ì§ì 주ì íë ë°©ë²ì¼ë¡ ì 1ì¼ê³¼ 2ì¼ì í¬ì¬íìë¤. ì´ìì 2주 ê°ê²©ì¼ë¡ ìííìë¤. ë°ìë¥ ì 2 ë´ì§ 3주기ì íììë² ìí í íê°íìê³ , ë¶ìì©ì NCI CTC ver. 2.0ì 기ì¤ì¼ë¡ íê°íìë¤. ê²°ê³¼: ì´ 35ëª íìë¤ì ì´ ìì¡´ê¸°ê° ì¤ìê°ì 8.5ê°ì(6.23-10.90ê°ì)ì´ìê³ , ë°ìì§ì기ê°ì 4.5ê°ì(0.38-9.75ê°ì)ì´ìë¤. ì¹ë£ë°ììì ìì ê´í´ë ììê³ , ë¶ë¶ê´í´ 19ì(54.3%), ë¶ë³ 13ì(37.1%), ì§í 3ì(8.6%)ìë¤. ì ì²´ íììë² 298í ì¤ grade 3 ì´ìì ë°±í구 ê°ìì¦ì 5í(1.6%)ìê³ , í¸ì¤êµ¬ ê°ìì¦ì ì´ 27í(9%)ìë¤. Grade 3 ì´ìì ë¹íì 4í(1.3%)ìê³ , íìí ê°ìì¦ì 10í(3.2%)ìë¤. í¸ì¤êµ¬ ê°ìì¦ì ìí ê°ì¼ì´ ìì´ 1ëª ì íìê° ì¬ë§íìë¤. Grade 1-2 ì ê²½ë³ì¦ì´ 44í(14.7%)ìì ëíë¬ë¤. ê²°ë¡ : FOLFOX-4ì ë³í©ííìë²ì ìì ì í ì ìë ì§íì± ìì íìë¤ì ëí 1ì°¨ ìë²ì¼ë¡ ëì ë°ìë¥ ì ë³´ì´ë©´ì ë ì±ì´ ì½í ë¹êµì ìì í ì¹ë£ë²ì´ë¤. ì¤ì¬ ë¨ì´: ìì; Oxaliplatin
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Hypersensitivity reaction (HSR) and sensory neuropathy are major complications of oxaliplatin-based chemotherapy. Preplanned withdrawal of oxaliplatin after the first six cycles and reintroduction at the time of disease progression (stop-and-go strategy) may reduce neurotoxicity. However, the effect of an oxaliplatin-free interval on HSR occurrence remains poorly understood.Data on patients with colorectal cancer who received FOLFOX (5-fluorouracil, leucovorin and oxaliplatin) treatment between June 2005 and June 2009 were retrieved from the prospective cohort database of the Outpatient Oncology Unit of the Kyoto University Hospital. Factor analysis was performed.Among patients who received six or fewer cycles of FOLFOX, the incidence of HSR was low (7/99, 7.1%). For patients who received more than six cycles, the incidence of HSR was higher among patients treated with stop-and-go FOLFOX than among patients treated with continuous FOLFOX (25/61, 41.0% vs. 13/63, 20.6%; p = 0.019). Interestingly, most cases of HSR during stop-and-go FOLFOX occurred during the second or third cycle of the reintroduction phase (21/25, 84%). Multivariate analysis identified undergoing an oxaliplatin-free interval as an independent risk factor (p = 0.016).An oxaliplatin-free interval may increase the risk of HSR. Special vigilance is needed during the second and third cycles after reintroduction of oxaliplatin.
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Oxaliplatin with 5-fluorouracil plus leucovorin (FOLFOX) has become the standard treatment in patients with colorectal cancer.Among known toxicities induced by oxaliplatin, hematological, gastrointestinal and neurological toxicities are common.However, acute pulmonary toxicity associated with oxaliplatin is unusual.One case of interstitial lung disease associated with the FOLFOX protocol is reported here.(
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瞄准：为了比较，加 cisplatin (PCF ) 与氟尿嘧啶相结合的 paclitaxel 的功效和安全，和 oxaliplatin 为先进胃的癌症(自动增益控制) 把正 leucovorin (FOLFOX-4 ) 政体与氟尿嘧啶相结合。方法：有自动增益控制的 94 个病人随机被分配在天收到 paclitaxel ( 50 mg/m2 iv ) 1 ， 8 和 15 ， cisplatin ( 20 mg/m2 iv )和天 1-5 上的氟尿嘧啶( 750 mg/m2 iv )，或 oxaliplatin ( 85 mg/m2 iv )和白天 1 上的 leucovorin ( 200 mg/m2 iv )，在天由大丸药氟尿嘧啶( 400 mg/m2 iv )和氟尿嘧啶( 600 mg/m2 iv )列在后面 1 和 2 。主要结束点是 1 年的幸存时间。结果：病人的全面反应率(ORR ) 分别地是 48.0% 和 45.5% 到 PCF 和 FOLFOX-4。PCF 和 FOLFOX-4 的疾病控制率(DCR ) 分别地是 82.0% 和 81.8% 。分别地，病人的中部的幸存时间(山区标准时间) 在有 PCF 和 FOLFOX-4 的治疗以后是 10.8 和 9.9 瞬间。分别地，病人的 1 年的幸存率在有 PCF 和 FOLFOX-4 的治疗以后是 36.0% 和 34.1% 。没有重要差别在在二个组之间的 ORR， DCR，山区标准时间或 1 年的幸存率被观察。最普通的不利事件是贫血症，恶心并且呕吐，并且在 PCF 的等级 3/4 脱发治疗组，和贫血症，分级 1/2 在 FOLFOX-4 治疗的毒害神经的效果和等级 3/4 嗜中性白血球减少症组。结论：有自动增益控制的病人让类似的回答与类似的幸存率评价到 PCF 和 FOLFOX-4 政体。PCF 和 FOLFOX-4 政体为自动增益控制象有希望的治疗有效、可容忍。
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目的：FOLFOX 是第三期大腸直腸癌術後標準輔助性化學治療。但是許多病人無法完成完整療程。本研究欲探討完成完整FOLFOX 療程的比率及其無法完成的原因。方法：由台北榮總大腸直腸外科資料庫收集2009 年一月至2015 年十二月第三期大腸直腸癌術後接受FOLFOX 治療之病人之基本資料、接受Oxaliplatin 之劑量及無法完成之原因做分析。結果：研究期間內內共866 個第三期大腸直腸癌病人接受手術。其中110 人沒有接受後續輔助性化學藥物治療，199 人接受其他療法，5 人於其他他醫院治療。最後收集572人分析。290 人 (50.6%) 完成完整療程，其Oxaliplatin 累計計劑量之中位數為984 mg/m^2(644~1210 mg/m^2)。無法完成完整療程的病人中，78 人 (27.7%) 是因為主治醫師預防性停藥，72 人 (25.5%) 因週邊神經病變，30 人 (10.6%) 因疾病進展更換療法，18 人 (6.4%)因對Oxaliplatin 過敏，19 人 (6.7%) 因為白血球過低過肝腎功能惡化，17 人 (6.0%) 因嚴重噁心嘔吐，12 人 (4.3%) 因為整體身體狀況變差，36 人 (12.8%) 自行要求停藥。因週邊神經病變而中斷治療的患者，其Oxaliplatin 的累積劑量中位數為746 mg/m^2，而因對Oxaliplatin 過敏中斷治療的患者，其累積劑量中位數為680.4 mg/m^2。結論：半數病人能完成完整療程，週邊神經病變及及醫師預防性停藥是無法完成完整療程之主因。研發預防或減緩週邊神經經病變副作用之化學治療方法應能增加完整療程達成率。
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4024 Background: Oxaliplatin combined with fluoropyrimidines is standard adjuvant therapy in stage III colon cancer and first-line therapy in stage IV colorectal cancer. Oxaliplatin can be reintroduced either at relapse, or after maintenance or after chemotherapy holidays. In this study we defined the sensitivity to oxaliplatin reintroduction based on the oxaliplatin-free interval. Methods: Stage IV pts entered in the OPTIMOX1 and 2 studies (FOLFOX4, FOLFOX7 followed by maintenance without oxaliplatin or chemotherapy holidays) and pts having relapsed after metastases surgery and neoadjuvant or adjuvant FOLFOX for resectable stage IV were eligible if they were rechallenged with FOLFOX. Endpoints were: survival from reintroduction according to interval between the last cycle of oxaliplatin first-line and reintroduction, survival and response at reintroduction according to first FOLFOX response and PFS. Results: 330 pts were included: male 60%, colon/rectum/both 62%/35%/2%, resectable/unresectable: 14%/86%, PS 0–1 / >1: 90%/10%, sites 1/>1: 57%/43%. 23 pts had adjuvant and 22 pts had neoadjuvant chemotherapy. 58 pts (18%) had FOLFOX reintroduction before progression. PFS/OS from reintroduction according to induction FOLFOX response were 8.7/19.5 mths if CR, 4.6/15.2 mths if PR, and 3.2/9.7 mths if SD (P=.0019/.01). PFS/OS from reintroduction according to induction FOLFOX PFS were 2.9/9.3 mths if PFS<6 mths, 4.6/14.7 mths if PFS 6–12 mths and 8.5/23.7 if PFS=12 mths. Table shows results according to intervals. There was no difference between 0–3 and 3–6 mths or 6–9 and 9–12 mths intervals. Conclusions: A prolonged interval between two FOLFOX therapies or a prolonged PFS at first-line FOLFOX predict the efficacy of oxaliplatin reintroduction. The interval between two FOLFOX therapies does not identify a completely refractory population. Resistance (PD rate) is divided by two at each 6 month intervals. [Table: see text] No significant financial relationships to disclose.
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［背景］Oxaliplatinは，日本で合成された第3 世代の白金錯体系の抗悪性腫瘍剤であり，欧米ではOxaliplatin と持続投与5-FU/LV 併用（FOLFOX 療法）が進行再発大腸癌に対する標準的な化学療法としての地位を確立し広く施行されている。本邦では，2005 年4 月にOxaliplatinが承認され，当院でも切除不能進行・再発大腸癌に対するfirst-lineの化学療法としてFOLFOX 療法を積極的に施行している。［方法］2005 年6 月より2007 年8 月までに切除不能進行・再発大腸癌に対し，first-line としてFOLFOX4 およびmFOLFOX6 を施行した23 例を対象とし，その効果・安全性を検討した。FOLFOX4 は13 例に，mFOLFOX6は10 例に施行された。［結果］奏効率は50.0％であり，全生存期間は17.4 か月であった。投与回数の中央値は8.0，Oxaliplatinのrelative dose intensityは74.5％である。有害事象は，血液毒性ではGrade 3 以上の白血球減少を4 例，好中球減少を12 例に認め，非血液毒性ではGrade 3 の消化器毒性を1 例，Grade 3 の末梢神経障害を1例に認めたのみであった。［結語］FOLFOX 療法は，日本人においても進行再発大腸癌に対するfirst-lineの化学療法として比較的高い奏効性と安全性をもつ治療法であることが確認された。
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Oxaliplatin with 5-fluorouracil plus leucovorin (FOLFOX) has become the standard treatment in patients with colorectal cancer. Among known toxicities induced by oxaliplatin, hematological, gastrointestinal and neurological toxicities are common. However, acute pulmonary toxicity associated with oxaliplatin is unusual. One case of interstitial lung disease associated with the FOLFOX protocol is reported here. (Korean J Gastroenterol 2010;55: 340-343)
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Background : Combinations of Fluorouracil (FU) and biomodulator Leucovorin (LV) established as a standard regimen for therapy of colorectal cancer with metastases. To give better antitumor activity in colorectal cancer therapy, oxaliplatin is combined with FU/LV and give significant improvement. Fluorouracil can only be given by intravenous administration. This limitation raised effort to find alternative drugs that can be given orally, such as capecitabine. Capecitabine is an oral FU prodrug, with high oral bioavailability, highly accumulated in neoplastic tissue to be converted in FU, and well tolerated. Some clinical studies revealed effectivity of capecitabine plus oxaliplatin (XELOX) compared to FU/LV plus oxaliplatin (FOLFOX). Objective : This article is aimed to compare non inferiority of XELOX to FOLFOX in colorectal cancer with metastases, viewed form primary outcomes and secondary outcomes. Results : XELOX was comparable to FOLFOX with some benefitsover FOLFOX. Conclusion : XELOX could be considered as FOLFOX replacement as a standard therapyfor colorectal cancer with metastases.
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