Lapatinib对发炎性乳癌有效

　　October 2, 2006 (伊斯坦堡) –- GlaxoSmithKline公司的实验新药lapatinib (Tycerb) 可能可以提供复发发炎性乳癌病患一个重要的选择；该研究之作者，以色列Chaim Sheba医学中心的Bella Kaufman医师在第31届欧洲内科肿瘤医学会(ESMO)会议中向记者表示，这些病患治疗选择有限，而此药的耐受度还不错。
　　
　　主要研究者，多伦多Sunnybrook健康中心的Maureen Trudeau医师在访谈中向Medscape表示，我们在这些妇女身上看到明显的反应，这些病患试过多种治疗方式，但是却一而再、再而三的复发，所以此药具有效力且毒性极低是令人感到鼓舞的；Trudeau医师说她希望看到lapatinib尽早使用于这些病患。
　　
　　在有关此研究发现对乳癌作用的讨论中，该段会议的共同主席Jules Bordet研究院的Martine Piccart医师表示这个是“非常小型且是假设性的”研究，但是她承认此药对发炎性乳癌有极高活性。
　　
　　Trudeau医师向Medscape表示，我想，在病患样本少这一点她是对的，但是这问题是一直存在的，因为发炎性乳癌仅占此类病患的1% 到2%，除非范围相当广大，否则不可能在短期内有够多的病患进行随机试验；我认为对此类病患来说，此一需求是无法满足的，这些病患即使服用Herceptin还是会相当快速地恶化。
　　
　　【发炎性乳癌的有限治疗选择】
　　Genentech公司的trastuzumab以商品名Herceptin贩售，是一种 ErbB2抑制剂，也用于发炎性乳癌；Lapatinib是一种口服的生物活性可逆 ErbB1 暨 ErbB2 抑制剂；在发表的分析中，研究者评估lapatinib用在发炎性乳癌复发病患或者曾以anthracycline治疗无效者之整体反应率。
　　
　　研究者共研究47位病患并将之分成两组(32位在第一组，15位在第二组)；在A组，包括ErbB2-阳性病患，44%对lapatinib有部分反应，6%有完整反应；在B组，包括ErbB1-阳性和ErbB2-阴性病患，6.7%对治疗有部分反应；研究者报告有证据显示70%病患在初诊断时有皮肤淋巴侵犯。
　　
　　研究者结论认为lapatinib 一般耐受良好，仅有等级1和 2的肠胃道和皮肤相关副作用；有5例死亡，不过研究者认为可能是因为疾病恶化所致。
　　
　　Trudeau医师在发表时表示，Lapatinib单一治疗对发炎性乳癌病患有临床活性；肿瘤过度表现之ErbB2有50%反应率，而肿瘤表现ErbB1者则有7%。
　　
　　发炎性乳癌影响较年轻的病患，特别是诊断时年纪未满50岁者，且存活率最差，考虑最常见的乳癌侵犯形式，35%的病患在诊断时有转移症状；Trudeau医师对Medscape强调，发炎性乳癌病患需纳入试验，这是需要彻底研究的一个族群。
　　
　　【无明显的心脏毒性】
　　在同一段会议的另一篇报告中，来自佛罗里达Jacksonville梅约诊所的Edith Perez医师，发表了有关lapatinib的心脏方面资料；任何以ErbB为标靶的制剂，都一定会有郁血性心脏衰竭或射出分率遽降之顾虑；Trudeau医师指出，trastuzumab与心脏问题有关。
　　
　　但是有一个令人惊讶的发现，研究者观察3500位被仔细监测的病患，仅有0.2%有心脏事件。
　　Perez医师表示，这可以说几乎没有发生率，这对一般病患才会有此期待，所以lapatinib的心脏安全性令我们印象深刻。
　　
　　Trudeau医师表示，她的团队对此药的心脏安全性有类似结果，据我们在此研究中所观察的病患，此一结果不令人惊讶，因为他们也没有问题；不过，Piccart医师警告这一新的心脏安全研究可能是受到选择偏见所致；她在此段会议后的讨论中指出，随机服用lapatinib这一个ErbB 抑制剂的许多病患，可能有强壮的心脏面对潜在的安全顾虑。
　　
　　Trudeau医师向Medscape表示，我认为lapatinib在未来是有用的，迟早会如Herceptin一般被更广泛使用；此药提供新的治疗，但是否比Herceptin更好或者这两者如何取舍作为第一线治疗，则仍有待确认。
　　
　　ESMO 31届会议：摘要140O 和142O。发表于 October 1, 2006。
　　

Lapatinib Shows Promise in Inflammatory Breast Cancer

By Allison Gandey
Medscape Medical News

October 2, 2006 (Istanbul) –- GlaxoSmithKline's experimental new drug lapatinib (Tycerb) may offer patients with recurrent inflammatory breast cancer an important alternative. "For these patients with limited options, it is very well tolerated," study author Bella Kaufman, MD, from the Chaim Sheba Medical Center in Tel Hashomer, Israel, told reporters here at the 31st Congress of the European Society of Medical Oncology (ESMO).




"We saw remarkable responses in these women," lead investigator Maureen Trudeau, MD, from the Sunnybrook Health Center in Toronto, Ontario, told Medscape during an interview. "These patients tried multiple therapies and they had relapsed and relapsed and relapsed, so for this to act on the tumor with minimal toxicity is very encouraging." Dr. Trudeau said she would like to see lapatinib started earlier in this patient population.



During a breast cancer discussion evaluating the findings, session cochair Martine Piccart, MD, from the Jules Bordet Institute in Brussels, Belgium, called the study "very small and hypothesis-generating." But she acknowledged that the drug does appear to be highly active in the setting of inflammatory breast cancer.



"I think she's right in that it's a small subset of patients," Dr. Trudeau told Medscape. "But that's always going to be the problem in inflammatory breast cancer because it's only 1% to 2% of the population. You're never going to have a large enough group in a short enough time to do a randomized study unless you did it quite widely. I think this demonstrates an unmet need in this group of patients, who may have rapidly progressive disease in spite of the availability of something like Herceptin."



Limited Treatment Options for Inflammatory Breast Cancer



Genentech's trastuzumab, sold under the brand name Herceptin, is an ErbB2 inhibitor and has been used in inflammatory breast cancer. Lapatinib is an orally bioavailable reversible ErbB1 and ErbB2 inhibitor. In the present analysis, the investigators evaluated the overall response rate to lapatinib in patients with inflammatory breast cancer with recurrent disease or who were refractory to prior anthracycline therapy.



The researchers looked at 47 patients divided into 2 cohorts (32 patients in the first group and 15 in the second). In Cohort A, which included ErbB2-positive subjects, they found that 44% experienced a partial response to lapatinib and 6% had a complete response. In Cohort B, which included ErbB1-positive and ErbB2-negative patients, they found that 6.7% experienced a partial response to therapy. The researchers reported that 70% of patients had evidence of dermal-lymphatic invasion at time of initial diagnosis.



The investigators conclude that lapatinib is generally well tolerated, with only grade 1 and 2 gastrointestinal and skin-related adverse events. There were 5 deaths in the cohort that the researchers say were most likely due to disease progression.



"Lapatinib monotherapy is clinically active in heavily pretreated inflammatory breast cancer patients," Dr. Trudeau said during her presentation. "There was a 50% response rate in tumors overexpressing ErbB2 and a 7% response rate in tumors expressing ErbB1."



Inflammatory breast cancer affects younger patients, most under the age of 50 years at diagnosis, and has the worst survival rate. Considered the most aggressive form of breast cancer, 35% of patients have metastatic disease at time of diagnosis. "Inflammatory breast cancer patients need to be in trials," Dr. Trudeau emphasized to Medscape. "This is a population that we need to thoroughly investigate."



No Apparent Cardiotoxicity



In another presentation at the same session, Edith Perez, MD, from the Mayo Clinic in Jacksonville, Florida, presented cardiac data for lapatinib. "There has always been a concern that anything that is ErbB targeted might be associated with congestive heart failure or large drops in ejection fractions," Dr. Trudeau said, noting that trastuzumab has been linked with heart problems.



But in a surprise finding, the researchers observed that in 3500 carefully monitored patients, only 0.2% experienced cardiac events. "This is really almost no incidence," Dr. Perez said. "I would have expected that in the general population, so we're very impressed by the cardiac safety of lapatinib."



Dr. Trudeau said her team had a similar experience with the cardiac safety of the drug. "In terms of the patients we've seen on study, this result is not surprising because they haven't had any problems either." But Dr. Piccart cautioned that this new cardiac safety study might be subject to selection bias. During a discussion following the session, she said that many of the patients randomized to lapatinib, an ErbB inhibitor, likely had strong hearts to begin with due to the potential safety concern.



"I think lapatinib is definitely going to be useful," Dr. Trudeau told Medscape. "I think in time it will be used more widely after Herceptin. It will provide a new therapy, but as for the comparison and whether it will prove to be better than Herceptin or how the 2 should be divided as first-line therapies remains to be determined."



ESMO 31st Congress: Abstracts 140O and 142O. Presented October 1, 2006.