作者：Roxanne Nelson
出處：WebMD醫學新聞
August 26, 2008 — 以Taxane為基礎的化學治療漸增，用於輔助治療早期和局部惡化乳癌，但是新研究認為這會有嚴重心理症狀風險；根據發表於8月1日癌症期刊的研究，相較於那些未使用taxanes的患者，接受 taxane為基礎治療的病患，情緒壓力嚴重惡化、心理恢復緩慢。
研究者也發現，接受taxane治療的病患，有臨床憂鬱的比率較高。
主要作者、俄亥俄州立大學壓力與免疫計畫中心博士後研究員Lisa Thornton博士向Medscape Oncology表示，目前，這些效應的潛在原因絕大多數還未確定，和那些未使用taxanes的患者相比，接受taxane治療的病患傾向有比較多令人心情不佳的症狀，如周邊神經病變。
不過，她指出，其資料認為，這些症狀無法解釋我們所發現的情緒恢復延遲的現象；病患並不是因為治療副作用而感到憂鬱。
另一個可能是潛在的免疫機轉；癌症治療，包括化學治療，會驅使發炎反應；發炎會產生類似憂鬱的症狀，包括心情低落、疲勞、易怒和失眠。Thornton博士表示，或許taxanes誘發的此一反應比其他藥物更強、更久；我們的其他資料顯示，taxanes會刺激免疫系統，所以這可能是未來要觀察的效應。
Thornton博士表示，除非我們知道更多可能的機轉，否則必須小心地為病患提供長期心情恢復時間諮商、在追蹤期間定期監控他們的心情、讓病患在需要時可以接受心理治療；此外，癌症存活者並未常規監控憂鬱症狀，且病患也不瞭解在治療後會有此症狀；如果他們知道，將可以顯著幫助他們妥善恢復；至於那些需要額外幫助者，心理治療對於癌症病患有效。
【增加情緒壓力與減緩心理恢復】
之前的臨床試驗發現，taxane治療時的生活品質降低，且不同於其他癌症治療；接受taxane治療的病患，其第三期試驗顯示有較差的社交和情緒功能；此案例控制研究的主要目標，是比較接受和未接受taxanes治療之乳癌患者的短期(治療期間)、中期(兩年)和長期(達五年)的毒性和生活品質。
此世代包括227名病患，在1994至2000年間有新診斷、手術治療的第二或三期乳癌，其中，55人處方中含有 taxanes，包括doxorubicin和cyclophosphamide與paclitaxel 的有45人、包括 doxorubicin和docetaxel的有5人，包括doxorubicin和cyclophosphamide與docetaxel的有5人。
三分之二的病患(n= 37)是在化療臨床試驗接受taxanes；其他是在標準規範外處方中接受taxanes (4個循環的 600 mg/m2 cyclophosphamide 與60 mg/m2 doxorubicin之後4個循環的175 mg/m2 paclitaxel)。
一如預期，接受taxane治療的病患有比較多的症狀，且比較可能因為毒性而延長化療療程(50% vs. 32%)；接受taxane治療的病患，在治療期間(於第4、8、12個月評估時)，9個徵兆中有6個症狀較多、較嚴重，不過，從第2至5年，這9個徵兆在這兩組病患並無差異。
研究者也觀察發現，接受taxane治療的病患，在治療期間明顯有較差的情緒壓力和生活品質，他們的心理恢復顯著較慢，平均需要兩年，而未使用taxane治療的病患只需要6至12個月。
接受taxane治療的病患，可能發生臨床憂鬱的比率也較高，特別的是，在第12和18個月時，兩組的憂鬱症狀之間有統計上的顯著差異，且一直到24個月時都還有此傾向；未使用taxane治療的病患，其可能憂鬱比率在12個月的追蹤時降低到不到10%，而taxane組的比率仍然偏高(將近20%)。
這項研究部分資金接受美國癌症學會、Longaberger公司的美國癌症學會乳癌研究資金、美國陸軍醫學研究 Acquisition Activity資金、國家心智健康研究中心、國家癌症研究中心、一般臨床研究中心、與俄亥俄州立大學綜合癌症中心贊助。研究者宣稱沒有相關資金上的往來。
Cancer. 2008;113:638-647.摘要。
Taxanes May Increase Risk for Significant Psychologic Symptoms
By Roxanne Nelson
Medscape Medical News
August 26, 2008 — Taxane-based chemotherapies are increasingly used for the adjuvant treatment of early and locally advanced breast cancer, but new research suggests that they confer a risk for significant psychologic symptoms. According to a study published in the August 1 issue of Cancer, patients who received taxane-based therapy had significantly worse emotional distress and slower psychologic recovery than those on a similar regimen without taxanes.
The researchers also observed high rates of probable clinical depression among patients who received taxane therapy.
Currently, the underlying reasons for these effects remain largely speculative, according to lead author Lisa Thornton, PhD, a post-doctoral fellow involved in the Stress and Immunity Cancer Project at Ohio State University, in Columbus. "Patients who receive taxanes do tend to have more of some types of symptoms, such as peripheral neuropathy, than patients on other chemotherapy medications, and those symptoms can be upsetting," she told Medscape Oncology.
"However, our data suggest that such symptoms cannot account for the delays in emotional recovery we saw with this group of patients," she added. "Patients were distressed beyond what would be expected based on their treatment side effects."
Another possibility is an underlying immunologic mechanism; cancer treatments, including chemotherapies, can trigger inflammatory reactions. Inflammation is known to produce depression-like symptoms, including low mood, fatigue, irritability, and sleeplessness. "It may be that taxanes trigger this response more strongly and for a longer period of time than other drugs do," said Dr. Thornton. "Other data from our lab suggest that taxanes do stimulate the immune system, so it's possible we may be seeing the after effects of that."
"Until we know more about the underlying mechanism, it would be prudent to counsel patients about the long emotional recovery time, monitor their mood as a routine part of follow-up, and make psychologic treatment available to patients who need it," said Dr. Thornton. "Also, depressive symptoms are not routinely monitored in cancer survivors, and patients may not realize their symptoms could be an after effect of treatment. If they know what to expect, that could significantly help people to cope with the recovery. And for those who need a little extra help, psychologic treatments have been shown to be effective for patients with cancer."
Increased Emotional Stress and Slower Psychologic Recovery
Findings from previous clinical trials have suggested that quality of life declines during taxane therapy, and the decline differs from that observed with other cancer treatments. Poorer social and emotional functioning have been reported in phase?3 trials among patients who received taxanes as part of their chemotherapeutic regimen than among those who did not receive them. The primary goal of this case–control study was to compare the short-term (during treatment), moderate-term (2 year), and long-term (up to 5 years) toxicity and quality of life among breast cancer patients who received taxanes and those who did not.
The cohort included 227 patients, accrued between 1994 and 2000, with newly diagnosed, surgically treated stage?2 or 3 breast cancer. Of this group, 55 received taxanes as part their treatment regimens, which included doxorubicin and cyclophosphamide with paclitaxel (n?= 45), doxorubicin and docetaxel (n?= 5), and doxorubicin and cyclophosphamide with docetaxel (n?= 5). Two thirds of the patients (n?= 37) receiving taxanes were participating in chemotherapy clinical trials; the others received taxanes as part of standardized off-protocol regimens (4 cycles of 600?mg/m2 cyclophosphamide and 60?mg/m2 doxorubicin, followed by 4 cycles of 175?mg/m2 paclitaxel).
As expected, patients who received taxanes experienced more symptoms and were more likely to have prolonged chemotherapy cycles because of toxicities (50% vs 32%). Patients receiving taxanes also experienced a greater number and severity of 6 of the 9 signs or symptoms assessed during their treatment period (4-, 8-, and 12-month assessments). However, from years 2 to 5, there were no differences observed between the 2 groups in any of the 9 signs or symptoms.
The researchers also observed that patients who received taxane agents had significantly worse emotional distress and mental quality of life throughout the treatment period. Their psychologic recovery was significantly slower, requiring an average of 2 years, compared with the 6 to 12 months required by patients who did not receive taxane.
The rates of probable clinical depression were also higher among patients receiving taxanes. In particular, there were statistically significant group differences in depressive symptoms at 12 and 18 months, and a trend toward such at 24 months. The rates of probable depression among patients who didn't receive taxanes declined to less than 10% by the 12-month follow-up, whereas the rates in the taxane group remained high (at approximately 20%).
The study was supported in part by grants from the American Cancer Society, by a Longaberger Company-American Cancer Society Grant for Breast Cancer Research, by US Army Medical Research Acquisition Activity grants, by the National Institutes of Mental Health, by the National Cancer Institute, by the General Clinical Research Center, and by the Ohio State University Comprehensive Cancer Center. The researchers have disclosed no relevant financial relationships.
Cancer. 2008;113:638-647. Abstract
[ 本帖最後由 goodcat1111 於 2008-9-6 19:40 編輯 ] |
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