本帖最後由 goodcat1111 於 2009-4-11 10:21 編輯
作者：Roxanne Nelson
出處：WebMD醫學新聞
March 26, 2009 — 三種藥物合併化學治療，相較於兩種藥物合併，可能增加咽喉與下咽喉癌症病患的咽喉功能。
在一項線上發表於3月24日國家癌症機構期刊的研究結果，法國研究者們報告在誘導期化學治療時接受cisplatin、docetaxel與5-fluorouracil（TPF），相較於僅接受cisplatin與5-fluorouracil（PF）治療的病患，更能夠保留咽喉功能。
在平均追蹤36個月時，接受TPF治療病患的咽喉功能保存率為70.3%，接受PF治療的病患則是57.5%。
病患接受cisplatin與5-fluorouracil誘導化學治療，這是罹患進展性咽喉或是咽喉下癌症病患接受完全咽喉切除術外的另一個選擇，接著，研究者對化學治療有反應的病患進行放射線治療。研究者們表示，最近以治癒為目的的臨床研究數據顯示，加上docetaxel增加了反應率與整體存活率。
在這項研究中，來自法國 Regional et Universitaire de Tours醫學中心的Gilles Calais醫師與其同事隨機分派了213位罹患進展性咽喉與咽喉下癌症病患接受TPF（共110位）或PF誘導性治療（共103位）。
以TPF為誘導化學治療的那一組，在第一天使用75 mg/m2的docetaxel、75 mg/m2的cisplatin，以及750 mg/m2 24小時持續輸注的5-fluorouracil，輸注5天；之間間隔21天，共進行3個週期。
PF組的病患在第一天與第五天接受100 mg/m2的cisplatin，以及1000 mg/m2的24小時持續輸注5-fluorouracil，之間間隔21天共進行三個週期。所有符合條件的病患在最後一個週期的化學治療後，在三到七週之間都接受放射線治療。
TPF組中有76.4%的病患計畫接受咽喉保留放射線治療（這些病患都是對誘導化學治療有反應者），在PF組則有61.2%（其中57位是有反應者，6位拒絕開刀）。
【反應率更高 但存活率沒有差異】
研究者們觀察到，TPF組病患對於化學治療的整體反應率比PF組病患好（80%相較於59.2%）。對於誘導化學治療沒有反應的病患，接受完全咽喉切除術以及頸部切片，手術在最後一次化學治療週期後三到七週進行。
他們表示，TPF組病患恢復到正常咽喉運動功能的比例較高（42.7%相較於29.1%；P=0.034），且這些病患中64.4%並沒有殘存腫瘤，而在PF組僅有35.8%病患無殘存腫瘤。
雖然TPF療程的誘導作用，在兩組之間的三年咽喉功能保存比例是顯著較高的，但是存活率並沒有顯著差異。在三年時，兩組的整體存活率為60%，然而，TPF組病患免於疾病存活率為58%，PF組病患則是44%，兩者之間14%的差異並未達到統計上差異（P=0.57與P=0.11）。
【兩組都有急性與晚期毒性】
兩組病患都有發生急性毒性，共有5位病患因為急性毒性死亡（TPF組有3位，PF組有2位）。TPF組病患發生第二級掉髮的比例（19.4%相較於2.0%），第四級中性球低下（31.5%相較於17.6%）的比例較高，且發生第三級感染的比例，例如中性球低下發熱（10.9%相較於5.8%）也是較高的。相較起來，PF組病患發生第三與第四級口腔炎（7.8%相較於4.6%）、第三級與第四級血小板低下（7.8%相較於1.8%）、第四級肌酐酸濃度上升（2.0%相較於0%）比例都比較高。
兩組病患也都有發生晚期毒性，TPF組病患有6.2%病患發生第四期咽喉毒性（兩位病患在誘導化學治療後接受化學放射線治療），PF組病患則有13.6%的病患發生這樣的毒性（三位病患在誘導化學治療後接受化學放射線治療）。研究者們表示，其他晚期毒性發生率在兩組之間是差不多的，而為了要進一步評估晚期作用，需要長期的後續追蹤。
作者們的結論是，這項研究被設計針對進展性咽喉與咽喉下癌症，這些研究發現不應該一般化到頭頸部癌症的所有部位。他們寫到，未來的研究應該被設計來比較使用TPF作為誘導方法與同時進行的差異，重點應該放在這些方法的功能性結果。
這項研究由法國頭頸部腫瘤放射治療團隊（GORTEC）贊助。
Three-Drug Induction Chemotherapy Increases Larynx Preservation
By Roxanne Nelson
Medscape Medical News
March 26, 2009 — Three-drug induction chemotherapy might increase the likelihood of preserving larynx function in patients with larynx and hypopharynx cancers, compared with a commonly used 2-drug regimen.
In a study published online March 24 in the Journal of the National Cancer Institute, French researchers report that patients who received docetaxel, cisplatin, and 5-fluorouracil (TPF) during induction chemotherapy were more likely to retain larynx function than those treated with cisplatin and 5-fluoruracil (PF).
At a median follow-up of 36 months, the estimated larynx preservation rate was 70.3% in the TPF-treated patients and 57.5% in the PF-treated patients.
Induction chemotherapy with cisplatin and 5-fluorouracil, followed by radiation therapy in patients who respond to chemotherapy, is an alternative approach to total laryngectomy for people with advanced malignancies of the larynx and hypopharynx. The researchers note that recent data from clinical trials conducted with a curative intent suggest that the addition of docetaxel increases both the response rate and overall survival.
In this trial, Gilles Calais, MD, from the Centre Hospitalier Regional et Universitaire de Tours, in France, and colleagues randomized 213 patients with advanced larynx and hypopharynx cancer to induction therapy with either TPF (n?= 110) or PF (n?= 103).
Induction chemotherapy for the TPF group consisted of 75?mg/m2 docetaxel on day?1, 75?mg/ m2 cisplatin at on day 1, and 750?mg /m2 5-fluorouracil by 24-hour continuous infusion for 5 days; 3 cycles with a 21-day interval were planned.
Patients in the PF group received 100?mg/m2 cisplatin on days 1 and 5, and 1000?mg/ m2 fluorouracil by 24-hour continuous infusion for 5 days for 3 cycles, with a 21-day interval. All eligible patients received radiotherapy between 3 and 7 weeks after the final cycle of chemotherapy.
Radiation therapy for larynx preservation was performed in 76.4% of patients in the TPF group (all were responders to induction chemotherapy) and in 61.2% of patients in the PF group (57 were responders, 6 refused surgery).
Better Response Seen, But No Survival Difference
The researchers observed that patients in the TPF group had a better overall response rate to chemotherapy than those in the PF group (80% vs 59.2%). Individuals who did not respond to induction chemotherapy underwent total laryngectomy with neck dissection, with surgery being performed 3 to 7 weeks after the last chemotherapy cycle.
They also noted that a greater percentage of patients in the TPF group recovered to normal larynx mobility (42.7% vs 29.1%, respectively; P?= .034), and no residual tumor was detected in 64.4% of patients in the TPF group and in 35.8% of patients in the PF group.
Although induction with the TPF regimen achieved a statistically significantly superior 3-year larynx-preservation rate, survival rates were similar between the 2 groups. At 3 years, overall survival was 60% in each group, whereas disease-free survival was 58% for TPF patients and 44% for PF patients. The 14% difference did not reach statistical significance (P?= 0.57 and P?= 0.11, respectively).
Acute and Late Toxicity Seen in Both Groups
Acute toxicity was observed in both groups. A total of 5 patients died from acute toxicity (3 in the TPF group and 2 in the PF group). Patients in the TPF group also experienced a higher degree of grade?2 alopecia (19.4% vs 2.0%), more grade?4 neutropenia (31.5% vs 17.6%), and more grade?3 infections, such as febrile neutropenia (10.9% vs 5.8%). In comparison, those in the PF group experienced more grade?3 and 4 stomatitis (7.8% vs 4.6%), more grade?3 and 4 thrombocytopenia (7.8% vs 1.8%), and more grade?4 creatinine elevation (2.0% vs 0%).
Late toxicity was seen in both groups, with grade?4 larynx toxicity experienced by 6.2% of patients in the TPF group (2 patients received concurrent chemoradiotherapy following induction) and in 13.6% of patients in the PF group (3 received concurrent chemoradiotherapy after induction). The researchers note that other late toxic effects were comparable between groups, and that long-term follow-up is necessary to further evaluate late toxicities.
As the study was designed for advanced cancers of the larynx and hypopharynx, the findings should not be generalized to all sites of advanced cancers of the head and neck, the authors conclude.
"Future trials should be designed to compare the concomitant schedule with the induction approach using TPF," they write. "Emphasis should be put on the functional results of these approaches."
The study was funded by the French Head and Neck Oncology Radiotherapy Group (GORTEC).
J Natl Cancer Inst. 2009;101:498-506. |
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