Temozolomide加上干擾素Alpha-2b對黑色素瘤有益


  July 29, 2004 - 根據7月號英國皮膚學期刊(British Journal of Dermatology)一項隨機分派試驗結果顯示,合併temozolomide與干擾素α2b(IFN-α2b)的耐受性良好,且可改善第4期轉移性黑色素瘤之存活率。
  
  澳洲Graz大學Erike Richtig醫師與他的同事們指出,第4期疾病儘管有不同的治療選擇,平均存活率仍非常低;合併許多不同細胞毒性藥物,是否會增加反應率或存活率至今仍有爭議,但是合併化學療法,毒性會增加卻是不爭的事實。
  
  在這個多中心、開放標記的試驗中,患有第4期轉移性黑色素瘤的29位男性與18位女性病患,被隨機分派到兩組;20位病患,第1天至第5天口服temozolomide 150 mg/m2,每28天一個週期,合併IFN-α2b 10 MIU/m2隔天使用(A組);另外27位病患,第1天至第5天口服temozolomide 150 mg/m2,每28天一個週期,合併固定劑量IFN-α2b 10MIU隔天使用(B組);受試者平均年齡為57.6歲(年齡介於34至74歲)。
  
  整體反應率為27.6%,5位(10.6%)病患產生完全消退,包括1位A組病患與4位B組病患,而且5位病患中2位(4.3%,2個都是B組)持續到最後一次追蹤;8位病患(17%)產生部分消退,包括6位A組病患與2位B組病患,而且這8位病患中3位(6.4%)持續到最後一次追蹤,包括2位A組病患與1位B組病患;此外,有3位(6.4%)疾病穩定的病患,1位是A組病患2位是B組病患。
  
  平均存活時間是14.5個月(95%信賴區間為10.0-19.0個月),在2個治療組群間沒有顯著差異;3個週期後存活率與反應率相關(P<.03)。32位病患完成3個週期治療後,7位(3位A組病患,4位B組病患)部份或是完全反應的平均存活率(30.6個月;95%信賴區間為19.1-42.0個月),相較於25位沒有反應的病患(13.7個月;95%信賴區間為26.3-47.9個月)來得好。整體而言,至少達到一個完全消退的病患存活率最長(37.1個月;95%信賴區間26.3-47.9個月),再來是至少達到一個部份反應的病患(17.4個月;95%信賴區間10.9-23.9個月)。
  
  試驗中,並未發生治療相關的死亡;主要的副作用是噁心、嘔吐、頭痛、白血球低下、血小板低下、肝臟功能酵素上升與神經學症狀;5位病患因為副作用而停止治療,包括神經學症狀(2位)、敗血症(1位)、腦溢血(1位)以及皮疹(1位)。
  
  研究人員指出,temozolomide與IFN-α2b合併療法,可簡單地投予並顯示可耐受的毒性;治療三個週期後,出現明顯的反應,這代表著顯著的存活上的好處。
  
  AESCA與澳洲社會安全機構協會贊助這項試驗。

Temozolomide Plus Interferon A

By Laurie Barclay, MD
Medscape Medical News

July 29, 2004 — The combination of temozolomide and interferon-α2b (IFN-α2b) is tolerable and may show a survival advantage in stage IV metastatic melanoma, according to the results of a randomized trial published in the July issue of the British Journal of Dermatology.

"In stage IV disease...median survival is very poor, despite various treatment options, ranging from 3.6 to 11.8 months," write Erika Richtig, MD, from the University of Graz in Austria, and colleagues. "It remains a matter of debate whether the combination of several cytotoxic agents may increase response rate or survival, but combined chemotherapy is defintely more toxic."

In this multicenter, open-label study, 29 male and 18 female patients with stage IV metastatic melanoma were centrally randomized to one of two groups. Twenty patients received temozolomide 150 mg/m2 on days 1 to 5 orally every 28 days, in combination with IFN-α2b 10 MIU/m2 every other day (group A), and 27 patients received temozolomide 150 mg/m2 on days 1 to 5 orally every 28 days, in combination with IFN-α2b in a fixed dose of 10 MIU every other day (group B). Mean age was 57.6 years (range, 34-74 years).

Overall response rate was 27.6%. Complete remission occurred in five patients (10.6%), including one patient in group A and four patients in group B, and persisted through the last follow-up in two of these five patients (4.3%, both in group B). Partial remission occurred in eight patients (17%), including six patients in group A and two patients in group B, and persisted through the last follow-up in three of these eight patients (6.4%), including two patients in group A and one patient in group B. Of three patients (6.4%) with stable disease, one patient was in group A and two patients were in group B.

Mean survival was 14.5 months (95% confidence interval [CI], 10.0 - 19.0 months) with no significant differences between treatment groups. Survival correlated with response after three cycles (P < .03). Of 32 patients who completed at least three cycles of therapy, seven patients (three in group A and four in group B) with a partial or complete response had significantly better mean survival (30.6 months; 95% CI, 19.1 - 42.0 months) than did 25 patients who did not respond (13.7 months; 95% CI, 9.2 - 18.3 months). Overall, survival was longest in patients with at least one complete remission (37.1 months; 95% CI, 26.3 - 47.9 months), followed by patients with at least one partial response (17.4 months; 95% CI, 10.9 - 23.9 months).

There were no treatment-related deaths. Major adverse events were nausea, vomiting, headache, leukopenia, thrombopenia, elevation of liver function enzymes, and neurologica symptoms. Five patients discontinued treatment because of adverse events, including neurologic symptoms (two patients), sepsis (one patient), brain hemorrhage (one patient), and exanthema (one patient).

"The combination of temozolomide and IFN-α2b can easily be administered and shows tolerable toxicity," the authors write. "When an objective response occurs after three cycles, it indicates a significant survival advantage."

AESCA and the Association of Austrian Social Security Institutions supported this study.

Br J Dermatol. 2004;151:91-98

Reviewed by Gary D. Vogin, MD

    
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