| Abstract: | 研究背景及目的:以順鉑(cisplatin)為主的化學治療在非小細胞肺癌有效,但是也引起相當大的腎臟毒性。經由收集24小時尿液測定肌氨酸廓清率還是相當廣用,雖然其要花較多時間及較不方便。而用Cockcroft及Gault(C-G)的估算方法則較簡單方便,而且有少部份外國學者建議其可用來替代24小時尿液測定肌氨酸廓清率.這次實驗的主要目的是來比較這兩種方法在我們的非小細胞肺癌病人接受以順鉑(cisplatin) 為主的化學治療,治療前及過程中其肌氨酸廓清率改變相對狀況.另外也可來看C-G的估算方法,是否能夠準確預測化學藥物劑量
研究方法:從民國88年1月至民國90年1月我們有92位非小細胞肺癌病人(58位男性,34位女性)完成6次以順鉑(cisplatin)為主的化學治療.治療前所有病人其24小時尿液測定肌氨酸廓清率都大於每分鐘60毫升。順鉑(cisplatin)化學藥物劑量為每28天一期,每次劑量為每平方公尺體表面積100毫克。為了排除干擾,我們移除了有全身性嚴重疾病及有服用藥物會干擾肌氨酸測量的病人。每次化學治療前我們會測量病人的身高及體重。同時我們會請病房護士記錄及收集24小時尿液量.當24小時尿液收集完畢,我們會同時抽血與尿液一起送檢,測量肌氨酸。每個病人每次化學治療前都會作測量,總共6次。如果其肌氨酸廓清率大於每分鐘60毫升,每次劑量為平方公尺體表面積100毫克。如果其肌氨酸廓清率每分鐘60至30毫升之間,每次劑量為平方公尺體表面積50毫克。另一方面我們也用C-G的估算方法來看是否與24小時尿液測定肌氨酸廓清率值相當
研究結果:病人男性平均年齡為63.8歲,女性平均年齡為58.2歲。男性平均年齡有意義的高於女性.如果以65歲為老年人來界定,男性有37人大於或等於65歲。女性有12人大於或等於65歲.全部病人實際測量肌氨酸廓清率平均為每分鐘85.2毫升。明顯有意義的高於用C-G的估算方法算出之值有每分鐘25.7毫升。若是以測量方法來看,不論全部病人,65歲以上病人,65歲以下病人,都是估算方法得到值來得低.而對男女性而言,實際測量肌氨酸廓清率並無有意義的差別。但是若用估算方法得到的肌氨酸廓清率,則是女性明顯有意義的高於男性。若是以年齡來看,不論是何種測量方法,都是65歲以下病人,肌氨酸廓清率值來得高。
不論是何種測量方法,肌氨酸廓清率值會隨著逐次化學治療而降低。而且65歲以上病人,65歲以下病人,兩組間並無有意義的差別(15.1 與19.9毫升) 。但是若是以肌氨酸廓清率平均為每分鐘60毫升當作分界來看,則65歲以上病人實際測量肌氨酸廓清率,有比較高的比率會小於每分鐘60毫升以下。實際測量肌氨酸廓清率值在化學治療中之前三次值,分別與第六次化學治療之前實際測量肌氨酸廓清率值來比較,顯示有意義的差別。而用C-G的估算方法肌氨酸廓清率值,只有第一次與第六次化學治療之前估算方法肌氨酸廓清率值來比較,顯示有意義的差別。
若是以肌氨酸廓清率平均為每分鐘60毫升當作分界來看,實際測量肌氨酸廓清率值與用C-G的估算方法肌氨酸廓清率值,都同時在每分鐘60毫升以上或是同時在每分鐘60毫升以下,而來選擇一樣藥物劑量,全部病人有51%一樣。 65歲以下病人有77.9%一樣。而65歲以上病人,只有26.6%一樣。
我們若是以簡單線性迴歸方法來看,實際測量肌氨酸廓清率值與用C-G的估算方法肌氨酸廓清率值,不論全部病人,65歲以上病人,65歲以下病人,都是有意義的。(亦既是當實際測量肌氨酸廓清率值降低時,用C-G的估算方法肌氨酸廓清率值也隨著降低。) 但是實際測量肌氨酸廓清率值約大於用C-G的估算方法肌氨酸廓清率值每分鐘25毫升以上。
結論:在我們的非小細胞肺癌病人接受以順鉑(cisplatin)為主的化學治療,經由收集24小時尿液測定肌氨酸清率還是相當有用。雖然其要花較多時間及較不方便。用C-G的估算方法肌氨酸廓清率值往往低估當實際測量肌氨酸廓清率值。其值大約差每分鐘25毫升。肌氨酸廓清率會隨著年齡變老而降低,因此老年人的肌氨酸廓清率會比年輕人低。肌氨酸廓清率值會隨著逐次化學治療而降低。而且年老病人比年輕病人肌氨酸廓清率下降,兩組間並無有意義的差別。若是以肌氨酸廓清率平均為每分鐘60毫升當作分界來看,因為年老病人其原本肌氨酸廓清率比較低,所以有比較高的比率會小於每分鐘60毫升以下。但是若用C-G的方法估算肌氨酸廓清率值,則有更大比率會小於每分鐘60毫升以下,造成化學藥物劑量使用不足。尤其是年老病人。
雖然實際測量肌氨酸廓清率值與用C-G的方法估算肌氨酸廓清率值,不論全部病人,65歲以上病人,65歲以下病人,都有正相關, 但是用C-G的估算法,往往低估,會造成化學藥物劑量使用不足。影響效果。
但是從另外一個角度來看,可以先用C-G的估算法來算算看。因其往往低估,如果肌氨酸廓清率值大於每分鐘60毫升以上,那麼我們的非小細胞肺癌病人接受以順鉑(cisplatin)為主的化學治療,就不需要收集24小時尿液,可以直接作化學治療。針對65歲以上病人,其用C-G的估算法肌氨酸廓清率值小於每分鐘60毫升以下,最好需要收集24小時尿液實際測量肌氨酸廓清率值,如此才可選擇適當化學藥物劑量。
Background and purpose: Cisplatin (CDDP)-based chemotherapy (C/T) is effective but causes nephrotoxicity in patients with Non-Small-Cell lung cancer (NSCLC). Measured creatinine clearance (CCr) with 24-hour urine collection is used popularly although it takes much time and causes much inconvenience. Estimated CCr with Cockcroft and Gault’s (C-G) method is useful, easy to use, and suggested as a good tool for the CCr measurement by some authors. We try to compare the CCr values by the measured and C-G’s estimated methods in the courses of CDDP-based C/T in our NSCLC patients. Could the C-G’s method predict the appropriate renal classification and drug dosage in our patients
Methods: We studied 92 patients (58 men, 34 women) with advanced NSCLC receiving CDDP-based C/T for 6 cycles from 1999, January to 2001, January. Before C/T all these patients had measured CCr no less than (≧) 60 ml/min. The dose of CDDP per cycle was 100 mg/m2 every 28 days. Interferences were excluded such as severe systemic diseases, or medication known to disturb the creatinine measurement. Their body weight and height were measured each time before each cycle of C/T. To obtain the measured CCr value, urine was collected for 24 hours with start and finish times recorded by the nurses. When urine collection was finished, serum and urine creatinine levels were measured simultaneously in all patients before C/T. Totally there were six measurements for each patient before every C/T. If measured CCr ≧60 ml/min, CDDP 100 mg/m2 would be given. If measured CCr decreased to 30 to 60 ml/min, dose of CDDP was reduced by 50%. We also calculate estimated CCr each time before C/T for comparison with measured CCr.
Results: The mean ages were 63.8±10.3 years old (y/o) for male, 58.2±10.4 y/o for female patients ( p < 0.01). Within the 58 male patients, 21 were less than (<) 65 y/o and 37 were ≧65 y/o. Of the 34 female patients 22 were <65 y/o. The mean value of measured CCr was 85.2 ml/min and is higher significantly from the mean estimated CCr with the difference 25.7 ml/min. From the viewpoints of methods, the values of CCr were significantly lower over the estimated methods in all the patients, and both groups patients either <65 y/o or ≧65 y/o. The values of measured CCr of male and female patients were not different significantly. But the values of estimated CCr were higher significantly in female patients. From the viewpoints of age, the values of CCr over the patients < 65 y/o were significant higher than patients ≧65 y/o in both methods. The CCr values reduced significantly during the six cycles of C/T in both the measured and estimated methods. It was not different significantly in patients <65 y/o or ≧65 y/o ( 19.9 ml vs 15.1 ml, p=0.07). But 13.4% of the patients ≧65 y/o and only 5.4% of the patients <65 y/o had the measured CCr down to <60 ml/min.(p <0.01).
The values of the first three of the measured method and the first one of the estimated method differed significantly from the CCr values of both methods before the 6th cycle of chemotherapy.
Using a cutoff value of measured CCr ≧60 or <60 ml/min, agreement of the dosage of chemotherapy agents between the measured and estimated methods were 51% for all patients, 77.9% for patients < 65 y/o and only 26.6% for patients ≧65 y/o. Simple linear regression method was used to examine the association between the measured and estimated methods with significant correlation for all patients, those <65 y/o or ≧65 y/o ( r=0.684, 0.636, 0.553, separately),but with the difference of CCr value about 25 ml/min (measured CCr — estimated CCr) .
Conclusions: Measured CCr with 24-hour urine collection is still useful for CDDP-based C/T in our NSCLC patients although it takes much time and causes much inconvenience. C-G’s formula usually underestimates the measured CCr for about 25 ml/min. The values of CCr are different significantly between the older and younger patients as the aging process. The CDDP-based C/T does reduce the value of CCr, but without significant difference between the older and younger patients. But as the older patients have lower baseline CCr values, it would be easier for them to be down to < 60 ml/min. But the estimated method would cause much more under dose problems significantly, especially for patients ≧65 y/o. Although the C-G’s method does have significant correlation with the measured method, it has limited clinical use especially for the proper dose of C/T agents. In another way of thinking, as C-G’s method usually underestimates measured CCr, it may be used as a screen for all our NSCLC patients receiving CDDP-based C/T. If the estimated values are ≧60 ml/min, then no more 24-hour urine collection is needed. For the patients ≧65 y/o, it is better to collect 24-hour urine for measured CCr before and during CDDP-based C/T if the estimated CCr is < 60 ml/min. This would prescribe appropriate doses for these patients. |
