Crown John P, Burris Harold A, Boyle Fran, Jones Suzanne, Koehler Maria, Newstat Beth O, Parikh Roma, Oliva Cristina, Preston Alaknanda, Byrne Julie, Chan Steve
St Vincent's University Hospital, Dublin, Ireland,
Breast Cancer Res Treat. 2008 Nov;112(2):317-25. doi: 10.1007/s10549-007-9860-9. Epub 2008 Jan 20.
To characterize diarrhea events in patients with cancer treated with lapatinib as monotherapy or in combination with capecitabine or taxanes.
Eleven clinical trials (phase I, II, or III) in patients with metastatic cancer were analyzed. Lapatinib was administered at doses ranging from 1,000 to 1,500 mg/day as monotherapy (n = 926) or in combination with capecitabine (n = 198) or taxanes (n = 687). Diarrhea events were characterized based on severity, time to onset, duration, required interventions, and clinical outcomes.
In the pooled analysis of nine studies, diarrhea occurred in 55% of lapatinib-treated patients and 24% of patients not receiving lapatinib. All grade diarrhea occurred in 51% of patients treated with lapatinib monotherapy and 65% treated with lapatinib plus capecitabine. In a separate analysis, 48% of patients treated with lapatinib plus a taxane experienced diarrhea. Overall, most diarrhea events were grade 1/2. Grade 3 events occurred in <10% of patients and grade 4 events were rare (<or=1%). Most diarrhea events resolved with conventional approaches and without dose modification. Approximately 40% of patients treated with lapatinib monotherapy or combination therapy experienced a first diarrhea event within 6 days of treatment initiation, with a median duration of 7-9 days. Lapatinib-containing chemotherapy regimens do not cause severe diarrhea when proactive monitoring and intervention is introduced.
Most diarrhea events in lapatinib-treated patients are low grade, requiring infrequent lapatinib dose modification or interruption. Proactive management of diarrhea is crucial to prevent more serious complications in lapatinib-treated patients.
对接受拉帕替尼单药治疗或与卡培他滨或紫杉烷联合治疗的癌症患者的腹泻事件进行特征描述。
分析了11项针对转移性癌症患者的临床试验（I期、II期或III期）。拉帕替尼的给药剂量为每日1000至1500毫克，作为单药治疗（n = 926）或与卡培他滨联合使用（n = 198）或与紫杉烷联合使用（n = 687）。根据严重程度、发病时间、持续时间、所需干预措施和临床结果对腹泻事件进行特征描述。
在9项研究的汇总分析中，接受拉帕替尼治疗的患者中有55%发生腹泻，未接受拉帕替尼治疗的患者中有24%发生腹泻。所有级别的腹泻在接受拉帕替尼单药治疗的患者中发生率为51%，在接受拉帕替尼加卡培他滨治疗的患者中发生率为65%。在另一项分析中，接受拉帕替尼加紫杉烷治疗的患者中有48%发生腹泻。总体而言，大多数腹泻事件为1/2级。3级事件发生在不到10%的患者中，4级事件很少见（≤1%）。大多数腹泻事件通过常规方法解决，无需调整剂量。接受拉帕替尼单药治疗或联合治疗的患者中，约40%在开始治疗后6天内出现首次腹泻事件，中位持续时间为7 - 9天。当引入主动监测和干预时，含拉帕替尼的化疗方案不会导致严重腹泻。
接受拉帕替尼治疗的患者中，大多数腹泻事件为低级别，很少需要调整拉帕替尼剂量或中断治疗。对腹泻进行主动管理对于预防接受拉帕替尼治疗的患者出现更严重的并发症至关重要。
