懷念睿寶貝 Memory for Ray baby

腫瘤專家經常使用化療藥物的組合作為抗腫瘤一拳擊倒。該戰略已證明是成功的，因為它的目的是堵塞機械癌細胞具有協同作用的方式，更有效地對抗癌症的藥物可能會比個人單獨。

聖裘德研究人員報告了初步試驗的一種新的藥物組合，有望成為治療兒童癌症類似。最初的試驗中的藥物合用草酸鉑和依托泊苷表明，該組合造成一些副作用。此外，第一階段的研究表明，16例患者聯合用藥的成效顯著對抗腦癌髓母細胞瘤和pineoblastoma。

一份報告，這項工作將出現在2月1日發行的期刊 癌症。

這兩種藥物攻擊癌細胞在互補的方式，說麗莎 McGregor醫師，博士，腫瘤科，該研究報告的第一作者。奧沙利鉑龍頭本身的DNA分子，構成了癌細胞的基因。它不僅阻止了基因的功能，但有助於阻止 細胞的DNA修復機制，從糾正損害。依托泊苷提供了第二次打擊阻斷的一個重要組成部分的DNA修復機制。

此前，腫瘤已成功地與化學相結合依托泊苷親屬奧沙利鉑，卡鉑，順鉑叫，治療兒童癌症。然而，這些藥物造成的副作用，包括腎臟和血細胞在骨髓中的毒性，以及聽力損失。奧沙利鉑是用來治療大腸癌的成人，但是它並沒有受到審判結合依托泊苷。

“奧沙利鉑沒有出現有任何腎毒性，不會造成聽力損失，也似乎沒有什麼影響了骨髓，”麥格雷戈說。 “這可以，但是，導致神經問題的形式刺痛和麻木的四肢和喉嚨，這是加劇了寒冷。在我們的第一階段研究中，我們試圖探索的副作用是什麼，可能是當奧沙利鉑(治療大腸癌用藥)與依托泊苷(白金第三代)結合。“

麥格雷戈和她的同事發現，標準劑量的奧沙利鉑和依托泊苷產生副作用最小的孩子誰接待了他們。但是，在更高的鉑劑量，有些患者出現了一些骨髓毒性。

“最稱心，我們確實看到的證據表明，治療工作的腦腫瘤患者，”麥格雷戈說。 “髓母細胞瘤1例復發了他的腫瘤縮小消失，1例腫瘤縮小 pineoblastoma有顯著的堅持。”

其他病人在審判和其他類型的癌症疾病的表現穩定，但這種穩定不能被稱為一個顯著的反應的治療。

由於最初的承諾是兩藥合用，研究人員正著手添加藥物環磷酰胺的奧沙利鉑，依托泊苷的組合。異環磷酰胺損害 DNA的方式有別於奧沙利鉑聯合行動，並會與其他兩種藥物來殺死癌細胞的快速增殖。目前，腫瘤科醫師用異環磷酰胺聯合卡鉑和依托泊苷治療復發癌症，而代以 奧沙利鉑可能減少副作用所造成的卡鉑，麥格雷戈說。

本文的其他作者包括謝裡 Spunt醫師，維克多桑塔納，醫師和韋恩弗曼博士，所有腫瘤;克林頓斯圖爾特，藥學博士，和Deborah區，藥學博士，都製藥科學;艾米沃特金斯，碩 士，生物統計;弗雷德Laningham醫師，放射科學和瑪麗亞姆 Fouladi醫師，以前的聖裘德。

贊助這項研究部分由美國公共衛生服務和ALSAC。

2009年3月

Oncologists frequently use combinations of chemotherapy drugs as a knockout punch against tumors. The strategy has proven successful because it aims to jam the machinery of cancer cells in ways that are synergistic—fighting cancers more effectively than the individual drugs could alone.

St. Jude researchers have reported initial trials of a new drug combination that promises to be a similar treatment for childhood cancers. The initial trials of the drug combination of oxaliplatin and etoposide showed that the combination caused few side effects. Furthermore, the phase 1 study in 16 patients showed the drug combination’s significant effectiveness against the brain cancers medulloblastoma and pineoblastoma.

A report on this work appears in the February 1 issue of the journal Cancer.

The two drugs attack cancer cells in complementary ways, said Lisa McGregor, MD, PhD, Oncology, the study’s first author. Oxaliplatin latches itself to DNA molecules that make up the cancer cells’ genes. It not only prevents the genes from functioning, but helps block the cells’ DNA repair machinery from correcting the damage. Etoposide provides a second blow by blocking a key component of that DNA repair machinery.

Previously, oncologists had successfully combined etoposide with chemical relatives of oxaliplatin, called carboplatin and cisplatin, to treat children’s cancers. However, those drugs cause side effects, including kidney and blood cell toxicity in the bone marrow, as well as hearing loss. Oxaliplatin is used to treat colorectal cancer in adults, but it had not been tried in combination with etoposide.

“Oxaliplatin does not appear to have any kidney toxicity, causes no hearing loss and also appears to have little effect on the bone marrow,” McGregor said. “It can, however, cause nerve problems in the form of tingling and numbness in the extremities and throat, which is aggravated by cold. In our phase 1 study, we sought to explore what the side effects might be when oxaliplatin is combined with etoposide.”

McGregor and her colleagues found that standard doses of oxaliplatin and etoposide produced minimal side effects in the children who received them. However, at a higher oxaliplatin dose, some patients showed some bone marrow toxicity.

“Most gratifyingly, we did see evidence that the treatment was working in the patients with brain tumors,” McGregor said. “One patient with recurrent medulloblastoma had his tumor shrink away, and one patient with pineoblastoma showed significant tumor shrinkage that persisted.”

Other patients in the trial with other cancer types showed stabilization of disease, but such stabilization cannot be termed a significant response to the treatment.

Given the initial promise of the two-drug combination, the researchers are now proceeding to add the drug ifosfamide to the oxaliplatin-etoposide combination. Ifosfamide damages DNA in a way distinct from oxaliplatin and would act in union with the other two drugs to kill the rapidly proliferating cancer cells. Currently, oncologists use ifosfamide in combination with carboplatin and etoposide to treat relapsed cancers, and substituting oxaliplatin might reduce the side effects caused by carboplatin, McGregor said.

Other authors of this paper include Sheri Spunt, MD, Victor Santana, MD, and Wayne Furman, MD, all of Oncology; Clinton Stewart, PharmD, and Deborah Ward, PharmD, both of Pharmaceutical Sciences; Amy Watkins, MS, of Biostatistics; Fred Laningham, MD, of Radiological Sciences, and Maryam Fouladi, MD, formerly of St. Jude.

This research was sponsored in part by the U.S. Public Health Service and ALSAC.

March 2009