Rituximab維持治療改善濾泡性淋巴瘤之整體存活


  May 21, 2009 — 根據一篇新的統合分析,對於濾泡性淋巴瘤病患,相較於觀察或在疾病惡化時給予藥物治療,維持以rituximab(Rituxan,Genentech藥廠;MabThera,Roche藥廠)治療可以顯著改善整體存活。
  
  線上登載於4月15日Cochrane Database of Systematic Reviews的統合分析作者寫道,因為有關rituximab對於此類病患之整體存活的資料不一致而進行此一研究。
  
  濾泡性淋巴瘤是一種B細胞非何杰金氏淋巴瘤,一般無痛或生長緩慢。
  
  以色列Rabin醫學中心內科的Liat Vidal醫師等作者建議,應將Rituximab維持治療加入成功誘導治療後復發或難治型濾泡性淋巴瘤病患的標準治療中。
  
  這篇統合分析大部份與Vidal醫師等人年初在美國國家癌症研究院期刊(2009:101:248-255)發表的相同,當時由Medscape Oncology報導。
  
  該分析共包含五個隨機試驗、985名病患,使用Rituximab維持治療者的整體存活,顯著優於那些隨機接受觀察或於惡化時才用rituximab治療者,(風險比[HR]為0.60;95%信心區間[CI]為0.45 - 0.79)。研究的平均追蹤範圍從26至41個月。
  
  不過,該分析發現,此藥物與較高的副作用比率有關,特別是感染。該分析對於一些有關rituximab的重要臨床問題也尚未解答,例如病患最受益與最適當的療程和處方為何。
  
  作者們也提到一個有關其發現的警告,五個試驗中有三個因為符合停止試驗的條件而提早終止。他們認為,這可能會曲解了統合分析的發現。他們寫道,統計理論與隨機試驗系統回顧的結果,因為明顯利益而提早停止,則可能因為系統性提早停止試驗而高估治療效果。
  
  作者們指出,有四篇未納入統合分析的隨機試驗目前還在進行中。
  
  他們也指出,Rituximab維持治療的臨床實務目前並未被主要指引所建議,例如國家綜合癌症網絡的指引。
  
  【次級結果】
  根據作者表示,濾泡性淋巴瘤佔約15%至30%的新診斷淋巴瘤,特徵是生長緩慢、初始反應率高,但是容易復發與惡化。
  
  多數病患出現末期疾病,實際上,統合分析中四個試驗的疾病分期資料中,85%至100%的病患屬於第III/IV期。
  
  除了整體存活這個主要結果,研究團隊檢視了次級結果,包括五個研究的無意外存活以及無惡化存活(Blood. 2006;108:4003-4008; Blood. 2004;103:4416-4423; J Clin Oncol. 2005;23:1088-1095; J Clin Oncol. 2007;25[18S]:8004; Ann Hematol. 2002;81:553-557)。
  
  Rituximab維持治療病患的無意外存活顯著優於那些隨機指派接受觀察者(HR, 0.46; 95% CI, 0.37 - 0.57),無惡化存活也顯著較佳(HR, 0.53, 95% CI 0.42 - 0.66)。
  
  【療程與誘導治療的差異】
  維持療程的次組分析中,作者們發現,不同rituximab療程之間,在結果上沒有統計上的顯著差異,不論是每六個月四次每週輸注、或者每二至三個月輸注一次。
  
  不過,相較於觀察組,儘管Rituximab維持治療有存活利益,在一篇比較Rituximab維持治療與惡化時給予rituximab的研究中,並未發現助益。作者們結論表示,還不清楚rituximab用於濾泡性淋巴瘤的適當時機與療程。
  
  這篇分析的限制之一是,事實上,這五個研究有不同的誘導治療。作者指出,因為這些試驗是在rituximab被視為濾泡性淋巴瘤病患之標準誘導治療的一部份前所進行,有些病患在誘導處方中並未接受rituximab。不過,他們表示,將rituximab納為誘導治療的一部份並未顯著改變結果。儘管在誘導治療與維持療程上有差異,但作者觀察發現,這些試驗傾向有相同的效果,這支持其結果的強度。
  
  【副作用】
  五篇試驗中有兩篇報告指出等級3/4副作用的比率,Rituximab維持治療組高於觀察組(相對風險[RR]為1.52;95% CI, 1.00 - 2.30)。Rituximab維持治療組病患的感染相關副作用顯著高於觀察組(RR,1.99;95% CI,1.21 - 3.27)。再者,嚴重感染副作用的風險也增加(RR,2.90;95% CI,1.24 - 6.76)。根據一篇研究結果,大多是耳朵、鼻子與喉嚨感染。這些類型感染的第3/4級患者都需要住院。
  
  研究者宣告沒有相關財務關係。
  

Rituximab Maintenance Improves Overall Survival in Follicular Lymphoma

By Nick Mulcahy
Medscape Medical News

May 21, 2009 — In patients with follicular lymphoma, rituximab (Rituxan, Genentech; MabThera, Roche) maintenance therapy significantly improves overall survival, compared with observation or treatment with the drug at the time of disease progression, according to a new meta-analysis.

The study was undertaken because of inconsistent data on rituximab and overall survival in this setting, write the authors of the meta-analysis, which was published online April 15 in the Cochrane Database of Systematic Reviews.

Follicular lymphoma is a B-cell non-Hodgkin's lymphoma that is typically indolent or slow-growing.

"Rituximab maintenance therapy should be added to the standard therapy of patients with relapsed or refractory follicular lymphoma following a successful induction treatment," advise the authors, led by Liat Vidal, MD, from the Department of Internal Medicine at the Rabin Medical Center in Petah-Tiqva, Israel.

The meta-analysis is largely the same as that published earlier this year by Dr. Vidal and others in the Journal of the National Cancer Institute (2009:101:248-255), which was reported by Medscape Oncology at the time.

In the analysis of 5 randomized trials with 985 patients, those treated with rituximab maintenance therapy had significantly better overall survival than those randomized to observation or to treatment with rituximab at progression (hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.45 - 0.79). The median follow-up in the studies ranged from 26 to 41 months.

However, the analysis found that the drug is associated with a higher rate of adverse events, particularly infections. The analysis also left important clinical questions about rituximab unanswered, such as the type of patients that benefit most and the optimal schedule and duration of treatment.

The authors also offered a considerable caveat about their findings: 3 of the 5 trials were terminated earlier than planned after meeting criteria set for stopping the trials. This may have skewed the findings of the meta-analysis, they suggest. "Statistical theories and the results of a systematic review of randomized trials stopped early for apparent benefit suggest that stopping trials early systematically overestimates treatment effects," they write.

Not included in the meta-analysis were 4 randomized trials currently underway, add the authors.

They also note that the practice of rituximab maintenance therapy is not currently recommended in major guidelines, such as those of the National Comprehensive Cancer Network.

Secondary Outcomes

Follicular lymphoma accounts for 15% to 30% of newly diagnosed lymphomas, according to the authors, and is characterized by slow growth, high initial response rate, but relapsing and progressive disease.

Most patients present with advanced disease and, indeed, in the 4 trials in the meta-analysis with disease-stage data, 85% to100% of the patients were stage?III/IV.

In addition to the primary outcome of overall survival, the study authors examined secondary outcomes, including event-free survival and progression-free survival in the 5 studies (Blood. 2006;108:4003-4008; Blood. 2004;103:4416-4423; J Clin Oncol. 2005;23:1088-1095; J Clin Oncol. 2007;25[18S]:8004; Ann Hematol. 2002;81:553-557).

Patients treated with rituximab maintenance therapy had significantly better event-free survival than those randomized to observation (HR, 0.46; 95% CI, 0.37 - 0.57), and significantly better progression-free survival (HR, 0.53, 95% CI 0.42 - 0.66).

Differences in Scheduling, Induction Therapy

In a subgroup analysis of maintenance schedules, the authors found that there was no statistically significant effect of the rituximab schedule — either as 4 weekly infusions every 6 months or as a single infusion every 2 to 3 months — on the outcomes.

However, despite the survival benefit of rituximab maintenance therapy, compared with observation, no benefit was seen in the 1 study in which rituximab maintenance and rituximab at progression were compared.

"The optimal timing and schedule of rituximab in follicular lymphoma is still unclear," conclude the authors.

One of the limitations of the analysis is the fact that the 5 studies had different induction therapies. Because the trials were conducted before rituximab was considered part of standard induction therapy for patients with follicular lymphoma, some of the patients did not receive rituximab as part of their induction regimen, note the authors. Nevertheless, the inclusion of rituximab as part of the induction protocol did not significantly change the outcomes, they say.

Despite the variations in induction therapy and the differences in maintenance schedules, "the trials tended to have the same effect," observe the authors, adding that this supports the "robustness" of their results.

Adverse Events

The rate of grade?3/4 adverse events was reported in 2 of the 5 trials, and was higher with rituximab maintenance therapy than with observation (relative risk [RR], 1.52; 95% CI, 1.00 - 2.30).

Patients in the rituximab-maintenance group had significantly more infection-related adverse effects than those in the observation group (RR, 1.99; 95% CI, 1.21 - 3.27). Furthermore, the risk was increased for severe infectious adverse events (RR, 2.90; 95% CI, 1.24 - 6.76). According to the results of 1 study, the infections were mostly of the ear, nose, and throat. Hospitalization was required for all patients with grade?3/4 infections of these types.

The researchers have disclosed no relevant financial relationships.

Cochrane Database Syst Rev. 2009;2:CD006552.

    
相關報導
EULAR 2009:無反應者再度以Rituximab治療類風濕性關節炎可達到反應
2009/6/26 上午 11:53:00
Rituximab應可用於濾泡性淋巴瘤之維持治療
2009/2/26 下午 03:39:00
Rituximab只對特定原發性進展型多發性硬化症患者有效
2008/9/30 下午 05:22:00

上一頁
   1   2   3  




回上一頁