作者：Roxanne Nelson
出處：WebMD醫學新聞
September 15, 2008 (瑞典斯德哥爾摩) — 研發中的藥物pazopanib (GlaxoSmithKline藥廠)，一種新的抗血管新生抑制劑顯示對於早期的非小細胞肺癌(NSCLC)病患有單一製劑活性；不過，這還是初步結果，他們認為此製劑對此類病患有高度活性，或許在治療肺癌上有所影響。
這個第二期研究的結果發表在第33屆歐洲腫瘤醫學會(ESMO)研討會中，顯示35名病患中有30人的腫瘤縮小，有一些案例的腫瘤減少達85%。
主持會議的ESMO主席、Jos? Baselga醫師表示，肺癌難以治療，新的製劑研發緩慢，這些結果相當令人鼓舞。
根據主要作者、紐約長老會醫院-Weill Cornell醫學中心胸腔外科主任、心臟胸腔外科教授Nasser Altorki醫師，標靶治療主要用在標準化學治療處方失敗的末期肺癌病患。
Altorki醫師在記者會中表示，我們希望證實的觀念是，我們可以在肺癌早期使用這些藥物，且對這些製劑的反應可以增加，因為此時期的癌症基因組成比較沒有複雜性。
早期肺癌一般以手術治療，沒有任何型式的術前治療；Altorki醫師解釋，當要使用適當的治療時，一般是化學治療，不論單一製劑或者併用製劑。就我所知，這是此藥物首次用於肺癌。
Pazopanib是一種研發中的口服血管新生抑制劑，針對血管上皮細胞生長因素受體，血小板源生長因素受體與c-kit受體；本研究之目的是使用標靶治療作為術前治療，且確認pazopanib的臨床和生物活性與安全性，在早期NSCLC病患術前給予此藥物。研究者也選定它作為單一治療，所以觀察到的任何反應都只與此藥物有關。
他表示，我們認為，如果pazopanib對腫瘤有效果，或許無法用標準測量方式偵測，因此，我們導入以腫瘤體積測量反應的觀念。
初步終點是腫瘤體積的變化，在pazopanib治療前後使用高解析度的電腦斷層掃描；次級終點包括RECIST(腫瘤反應評估標準)和安全性，分析治療前後的血漿樣本，以讓研究者校正腫瘤體積變化時的細胞激素/血管新生因素改變。
Altorki醫師表示，監測血漿樣本的變化幫助我們預測哪些病患對此治療最有反應。
全部35位病患中，60%有肺腺瘤，11%有鱗狀細胞瘤，29% 有其他類型的NSCLC；29名病患屬於第 Ia期疾病，20人屬於第Ib期疾病，13 人屬於第 IIa 期疾病，1 人屬於第Iib期疾病；術前(切片後)2-6週，每天一次Pazopanib 800 mg，之後為7天的排除期，平均治療期間為16天。
Altorki醫師表示，約有86% 的病患腫瘤縮小，縮小最多達腫瘤體積的85%；當你考量平均治療期間只有兩週，縮小的腫瘤體積的確相當令人印象深刻。
此藥物一般耐受良好，研究期間有5名病患出現等級3的毒性反應，包括高血壓、紅疹和嗜中性白血球減少症。
Altorki醫師強調，除了使用 pazopanib作為術前單一治療之外，該研究也提出測量腫瘤體積的新的3D影像技術，另一特色是在治療前後收集血漿樣本。
早期NSCLC可以用手術治癒，Altorki 醫師指出，接受試驗的病患除了對研究貢獻之外，並未預期有治療利益；依舊有接受實驗藥物而使得可以用手術治癒的疾病延緩數週進行治療的倫理問題。
Altorki醫師表示，你盡可能向病患解釋研究的潛在原因，但是大多時候，他們參與的理由是為了利他。
Baselga醫師從另一個角度看這些結果，指出手術前腫瘤縮小的好處：可以實際幫助外科醫師的手術，你可以有一種沒有毒性的治療且之後增加手術的便利性和治癒，此研究在許多領域都有深刻涵義。
以這些資料為基礎，計畫進行許多運用pazopanib於不同時期NSCLC 的研究，有些設定再將此藥物作為輔助治療。
第33屆歐洲腫瘤醫學會(ESMO) 研討會：摘要225O。發表於2008年9月15日。
Pazopanib Shows Encouraging Activity in Early-Stage Lung Cancer
By Roxanne Nelson
Medscape Medical News
September 15, 2008 (Stockholm, Sweden) — The investigational drug pazopanib (GlaxoSmithKline), a novel antiogenesis inhibitor, demonstrated single-agent activity in patients with early-stage non-small-cell lung cancer (NSCLC). Although the results are preliminary, they suggest that this agent is highly active in this setting, and might have a role in the treatment of lung cancer.
The results of this phase?2 study, which were presented here at the 33rd European Society for Medical Oncology (ESMO) Congress, showed that 30 of 35 patients experienced tumor shrinkage. In some cases, tumor size decreased by up to 85%.
"Lung cancer is difficult to treat, and new and novel agents have been slow in coming," commented Jos?Baselga, MD, the current president of ESMO. "These results are encouraging."
Targeted therapies are primarily used in patients with advanced lung cancer who have already failed standard chemotherapeutic regimens, according to lead author Nasser Altorki, MD, professor of cardiothoracic surgery and director of the division of thoracic surgery at New York Presbyterianeill Cornell Medical Center, in New York.
"The concept that we hoped to prove is that we can use these drugs during an early stage of lung cancer, and response to these agents may be increased because there is less complexity to the genetic make-up of their cancer," said Dr. Altorki during a press conference.
Early-stage lung cancer is generally treated surgically, without any type of preoperative therapy. When preoperative treatment is used, it is generally chemotherapy, either alone or in combination with other agents, explained Dr. Altorki. "To my knowledge, this is the first time that this drug has been used in lung cancer."
Pazopanib is an investigational oral angiogenesis inhibitor that targets vascular endothelial growth-factor receptor, platelet-derived growth-factor receptor, and c-kit. The objective of this study was to use targeted therapy as a preoperative treatment, and to determine the clinical and biologic activity and the safety of pazopanib, given preoperatively, in early-stage NSCLC patients. The researchers also elected to give it as monotherapy, so that any observed response could be attributed only to this intervention.
"We thought that if pazopanib had an effect on the tumor, it may not be detectable by standard measurements," he said. "Therefore, we introduced the concept of measuring response by tumor volume."
The primary end point was tumor-volume change, which was assessed by high-resolution computed tomography performed before and after pazopanib treatment. Secondary end points included RECIST response and safety, and analysis of pre-and post-treatment plasma samples allowed the researchers to correlate cytokines/angiogenic factors with changes in tumor volume.
"Monitoring changes in plasma samples might help us predict which patients are most likely to respond to this therapy," Dr. Altorki said.
Of the 35 patients in the cohort, 60% had adenocarcinoma, 11% had squamous cell carcinoma, and 29% had another type of NSCLC. There were 29 patients with stage?Ia disease, 20 with stage?Ib disease, 13 with stage?IIa disease, and 1 with stage?IIb disease. Pazopanib 800?mg QD was administered for 2 to 6 weeks before surgery (and after biopsy), and was then followed by a 7-day washout period. The median duration of therapy was 16 days.
"Roughly 86% of patients had a reduction in tumor size, and it was as much as 85% of the tumor volume," said Dr. Altorki. "When you consider that the median duration of treatment was only 2 weeks, that amount of reduction in tumor volume is really very impressive."
The drug was generally well tolerated, with grade?3 toxicities reported in 5 patients during the study period. These included hypertension, rash, and neutropenia.
Dr. Altorki emphasized that aside from using pazopanib as preoperative monotherapy, the study was novel because innovative imaging techniques were used to measure exact tumor volume as a 3D object, and because plasma samples were collected before and after treatment.
Early-stage NSCLC can be cured with surgery, and Dr. Altorki pointed out that the patients entered the trial without any expectation of benefit, other than contributing to research. There are questions of ethics related to the delay of potentially curative surgery by a few weeks to research an experimental drug.
"You do your best to explain the underlying reasons for the study to the patient, but most of the time, their reasons for participating are altruistic," Dr. Altorki said.
Looking at these results from another angle, Dr. Baselga pointed out the benefit of shrinking the tumor before surgery: "This can really facilitate the work of the surgeons, if you can give a nontoxic therapy and then increase the ease of surgery and a cure," he said. "This study has profound implications in many areas."
On the basis of these data, more studies with pazopanib in multiple stages of NSCLC are being planned, with some aimed at using the drug in an adjuvant setting.
33rd European Society of Medical Oncology (ESMO) Congress: Abstract 225O. Presented September 15, 2008.
[ 本帖最後由 goodcat1111 於 2008-9-23 21:57 編輯 ] |
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