作者：Roxanne Nelson
出處：WebMD醫學新聞
September 15, 2008（瑞典斯德哥爾摩）－研究者於第33屆歐洲腫瘤醫學會年會中報告，以交替治療療程包括化學治療與放射線治療，加上cetuxiimab，處理局部進展性頭頸部癌症，其研究結果是有潛力的。在這群病患中，可評估的受試者都有反應，除了局部皮膚炎的高發生率之外，其毒性與該族群使用化學治療及放射線治療所觀察到的差不多。
比利時Libre de Bruxelles大學腫瘤學教授、同時也是歐洲癌症研究與治療組織總裁Martine Piccart-Gebhart醫師表示，這些研究結果是非常有潛力的，現在我們必須進行一項大型研究來證實這些結果是無誤的。
研究作者、來自義大利柯奈爾S. Croce綜合醫院的Marco Merland醫師指出，頭頸部癌症的治療在過去幾十年來已經有長足進步，且治療選擇越來越多，我們確實需要各學門的整合治療。
結合化學治療藥物，例如鉑金類藥物，fluorouracil或是cetuximab，以及放射線治療已經證實對於局部頭頸部癌症有效，但是該療程與毒性有關。然而，Merlano醫師解釋，交替化學治療和放射線治療已經證實與僅使用放射線治療的毒性相似。
快速輪替的化學療法與放射線治療是同時進行化學放射線治療的變異，在這項第二期臨床研究中，Merland醫師與其同事評估45位罹患來自咽喉、口腔與咽喉下的扁皮惡性腫瘤，接受輪替治療的效果與毒性，大部分的病患（84%）罹患第四期疾病。
化學治療包括了20 mg/m2的carboplatin 20 mg/m2、fluorouracil 200 mg/m2，在第1、4、7週從第1天投予到第5天；放射線治療以每週10葛雷，在第2、5、8週，每日分成5次投予，最多達70葛雷。除此之外，在合併療法時每週加上cetuximab（Erbitux，ImClone系統有限公司/必治妥/默克KGaA）。
研究者於第3個月時評估對於治療的反應，共有40位病患接受完整的反應評估（其中1位病患拒絕接受評估，而另一位病患過早接受評估）。30位病患觀察到完全反應，10位病患觀察到部分反應。在這個族群中，免於惡化的存活時間超過21個月，而整體存活時間超過23個月。
毒性的發生機率是相當高的，65%病患發生第三級的口腔炎，29%病患發生第三級的敗血症/肺炎。發生第三級血液毒性的機率也顯著較高，其中3位病患死於相關毒性。
雖然研究者同意這些不良反應一樣可以在頭頸部癌症化學放射線治療上看到，但很大百分比的病患意外地罹患皮膚炎。32位病患罹患第三級局部皮膚炎（佔該族群71%），11位（24%）病患發生第二級皮膚炎。僅有2位病患（4%）發生全身性紅疹。
在這項研究的討論會中，紐西蘭Nijmegen Radboud大學Nijmegen醫學中心的Carla van Herpen醫師，他對於毒性相關死亡事件的高比率感到擔憂；她表示，因毒性事件而死亡的事件在第二期臨床研究通常是很低的，因為受試者挑選地比第三期臨床研究嚴，因此，在第三期臨床研究中，毒性反應的數字將會更高。
Alternating Treatment Regimen Shows Promise in Head and Neck Cancer
By Roxanne Nelson
Medscape Medical News
September 15, 2008 (Stockholm, Sweden) — Treating locally advanced head and neck cancers with an alternating regimen of chemotherapy and radiotherapy, in addition to cetuximab, has demonstrated promising results, researchers reported here at the 33rd European Society for Medical Oncology Congress. All of the evaluable patients in the cohort experienced a response and, aside from a high rate of localized dermatitis, toxicities were in the range of those generally observed with chemotherapy and radiotherapy in this population.
"These results are very promising but they are not controlled," commented Martine Piccart-Gebhart, MD, PhD, professor of oncology at the Universit?Libre de Bruxelles, in Belgium, and current president of the European Organisation for Research and Treatment of Cancer. "Now we must set up a large trial to prove that these results are valid."
Treatment for head and neck cancer has evolved over the past decade and an increasing number of options have emerged. "The treatment of head and neck cancer requires the cooperation of many specialties," said study author Marco Merlano, MD, from the S. Croce General Hospital, in Cuneo, Italy. "We really need a multidisciplinary approach."
Combining chemotherapeutic agents, such as platinum, fluorouracil, or cetuximab, with concurrent radiotherapy has shown activity in locally advanced head and neck cancers, but the regimen is associated with excessive toxicity. However, explained Dr. Merlano, treatment with alternating chemotherapy and radiation has demonstrated a toxicity profile that is similar to that of radiation therapy alone.
Rapidly alternating chemotherapy and radiotherapy is a variation of concurrent chemoradiation, and in this phase?2 trial, Dr. Merlano and colleagues evaluated the efficacy and toxicity of alternating treatment in 45 patients with squamous cell carcinoma tumors arising from the larynx, oral cavity, oropharynx, and hypopharynx. The majority of patients (84%) had stage?4 disease.
Chemotherapy consisted of 20?mg/m2 carboplatin and 200?mg/m2 fluorouracil, administered from day 1?to day?5 on weeks 1, 4, and 7. Radiation therapy consisted of 10?Gy/week in 5 daily fractions on weeks 2?, 5?, and 8?0, up to 70?Gy. In addition, cetuximab (Erbitux, ImClone Systems Inc/Bristol-Myers Squibb/Merck KGaA) was added every week during the combination therapy.
The researchers assessed patient response to the therapy at 3 months, and 40 patients were available for a full evaluation of response (1 patient refused and it was too early to assess another patient). A complete response was observed in 30 patients, and a partial response in 10 patients. Progression-free survival was more than 21 months and overall survival was more than 23 months in this cohort.
The rate of toxicity was fairly high, with 65% experiencing grade?3? stomatitis and 29% experiencing grade 3? sepsis/pneumonia. There were also a significant number of grade?3? hematologic adverse events, and 3?patient deaths were related to toxicity.
Although the researchers agree that these adverse events are in line with what can be expected with chemoradiation in head and neck cancer, the large percentage of patients with dermatitis came as a surprise. Grade?3 localized dermatitis was experienced by 32 patients (71% of the cohort), and grade?2 dermatitis was experienced by 11 patients (24%). Only 2 patients (4%) experienced a systemic rash.
During a discussion of the study, Carla van Herpen, MD, from Radboud University Nijmegen Medical Center, in Nijmegen, the Netherlands, expressed concern about the high rate of toxic deaths. "Toxic deaths are usually lower in phase?2 trials because the patient population is more selected than in a phase?3 study," she said. "In a phase?3 trial, then, this rate may be even higher."
33rd European Society of Medical Oncology (ESMO) Congress: Abstract 694PD. Presented September 14, 2008.
[ 本帖最後由 goodcat1111 於 2008-9-24 22:30 編輯 ] |
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