Alternate dosing of cetuximab for patients with metastatic colorectal cancer.

Joleen M Hubbard, Steven R Alberts
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Abstract

Background: Many chemotherapeutic regimens used to treat colorectal cancer (CRC), including 5-fluorouracil plus leucovorin in combination with irinotecan (FOLFIRI) or oxaliplatin (FOLFOX), are administered on an every-other-week (q2w) dosing schedule. Chemotherapy in combination with a monoclonal antibody (mAb) directed toward the epidermal growth factor receptor (EGFR) has emerged as an effective treatment option. There are currently 2 anti-EGFR mAbs approved by the United States Food and Drug Administration: cetuximab and panitumumab. Mutations of KRAS, a downstream protein in the EGFR pathway, predict resistance to EGFR mAbs. Thus, cetuximab and panitumumab are indicated for patients without a KRAS mutation (KRAS wild-type). Whereas panitumumab is approved on a q2w dosing schedule, cetuximab is approved as a weekly dose. However, only cetuximab is approved with FOLFIRI for frontline metastatic CRC, whereas panitumumab is approved for third-line. Because concomitant therapies are often administered q2w, the weekly dosing of cetuximab results in additional medical office visits.

Design: Several studies have assessed the safety and efficacy of cetuximab q2w. For this review, a comprehensive literature search of studies evaluating cetuximab q2w dosing was conducted. Safety and efficacy results of these trials and retrospective analyses were summarized and reviewed.

Results: In general, results with cetuximab q2w were comparable to those obtained with the weekly regimen.

Conclusion: These data suggest that for patients for whom weekly treatment with cetuximab presents a substantial burden to their quality of life, q2w dosing of cetuximab is a viable treatment option with a benefit:risk profile similar to that of the weekly regimen.

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西妥昔单抗在转移性结直肠癌患者中的替代剂量。
背景:许多用于治疗结直肠癌(CRC)的化疗方案,包括5-氟尿嘧啶加亚叶酸钙联合伊立替康(FOLFIRI)或奥沙利铂(FOLFOX),每隔一周(q2w)给药。化疗联合针对表皮生长因子受体(EGFR)的单克隆抗体(mAb)已成为一种有效的治疗选择。目前,美国食品和药物管理局批准了两种抗egfr单克隆抗体:西妥昔单抗和帕尼单抗。KRAS (EGFR通路中的下游蛋白)的突变可以预测对EGFR单克隆抗体的耐药性。因此,西妥昔单抗和帕尼单抗适用于没有KRAS突变(KRAS野生型)的患者。帕尼单抗被批准为每季度给药一次,而西妥昔单抗被批准为每周给药一次。然而,只有西妥昔单抗和FOLFIRI被批准用于一线转移性CRC,而帕尼单抗被批准用于三线。由于伴随治疗通常每两周进行一次,每周给药西妥昔单抗会导致额外的医疗办公室就诊。设计:几项研究评估了西妥昔单抗q2w的安全性和有效性。在本综述中,我们对评价西妥昔单抗q2w剂量的研究进行了全面的文献检索。对这些试验的安全性和有效性结果以及回顾性分析进行了总结和回顾。结果:总的来说,西妥昔单抗q2w治疗的结果与每周治疗的结果相当。结论:这些数据表明,对于每周接受西妥昔单抗治疗对其生活质量造成重大负担的患者,每2周给药西妥昔单抗是一种可行的治疗选择,其获益:风险概况与每周方案相似。
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