Sugarbaker Paul H, Stuart O Anthony, Carmignani C Pablo
Program in Peritoneal Surface Malignancy, Washington Cancer Institute, 106 Irving St. NW, POB 3900, Washington DC, 20010, USA.
Cancer Chemother Pharmacol. 2006 May;57(5):703-8. doi: 10.1007/s00280-005-0074-8. Epub 2005 Aug 11.
The rationale supporting the use of intraperitoneal chemotherapy in peritoneal surface malignancy relates to a large local-regional effect and low systemic toxicity. While optimizing the use of this treatment strategy, little information regarding the effect of volume of chemotherapy solution is available.
The goal of this study was to provide data regarding the effect of volume of chemotherapy solution on the pharmacokinetics of intraperitoneal chemotherapy. Data by which to optimally adjust this parameter during intraperitoneal chemotherapy treatments were sought.
Forty-eight patients with peritoneal surface malignancy were treated with hyperthermic intraperitoneal mitomycin C chemotherapy after a complete cytoreduction to remove all visible evidence of mucinous tumor. The dose of mitomycin C was always 12.5 mg/m(2) in males and 10 mg/m(2) in females. The first 12 patients were treated with 6 l of 1.5% dextrose peritoneal dialysis solution. The next 14 patients were treated with 4 l of fluid and then ten patients were treated with 2 l. In the last 12 patients the volume of fluid was 1.5 l/m(2) . Blood, peritoneal fluid, and urine samples were obtained every 15 min for 90 min; additional blood and urine samples were obtained at 120 min. Mitomycin C concentrations, urine volumes, and final intraperitoneal fluid volume were obtained.
The intraperitoneal and the plasma concentrations were highest in the 2-l group, less in the 4-l group, and least in the 6-l group. All differences were statistically significant. Also, the percent of mitomycin C absorbed decreased significantly from 2, to 4, to 6 l of fluid. The area under the curve (AUC) ratio of intraperitoneal concentration times time to intravenous concentration times time was 27.01+/-4.92 for 2 l, 22.22+/-7.95 for 4 l, and 24.01+/-8.46 for 6 l. These differences were not statistically significant. If both the volume of chemotherapy solution and the total dose of mitomycin C were determined from the body surface area, the pharmacokinetics of intraperitoneal mitomycin C were more consistent.
In order to prescribe a uniform treatment for patients receiving hyperthermic intraperitoneal mitomycin C, the total dose of the drug and the total volume of chemotherapy solution should be determined from the body surface area. If the volume of chemotherapy solution is not based on patient body surface area, predictions regarding toxicity are less precise.
支持在腹膜表面恶性肿瘤中使用腹腔内化疗的理论依据是其具有较大的局部区域效应和较低的全身毒性。在优化这种治疗策略的使用时，关于化疗溶液体积的影响的信息很少。
本研究的目的是提供有关化疗溶液体积对腹腔内化疗药代动力学影响的数据。寻求在腹腔内化疗治疗期间最佳调整该参数的数据。
48例腹膜表面恶性肿瘤患者在完全细胞减灭以清除所有可见的黏液性肿瘤证据后，接受了腹腔内热灌注丝裂霉素C化疗。男性丝裂霉素C的剂量始终为12.5mg/m²，女性为10mg/m²。前12例患者用6L 1.5%葡萄糖腹膜透析液治疗。接下来的14例患者用4L液体治疗，然后10例患者用2L治疗。在最后12例患者中，液体体积为1.5L/m²。在90分钟内每隔15分钟采集血液、腹膜液和尿液样本；在120分钟时采集额外的血液和尿液样本。获得丝裂霉素C浓度、尿量和最终腹腔内液体体积。
2L组的腹腔内和血浆浓度最高，4L组次之，6L组最低。所有差异均具有统计学意义。此外，丝裂霉素C的吸收百分比从2L到4L再到6L液体显著降低。腹腔内浓度乘以时间与静脉内浓度乘以时间的曲线下面积（AUC）比值，2L组为27.01±4.92，4L组为22.22±7.95，6L组为24.01±8.46。这些差异无统计学意义。如果化疗溶液的体积和丝裂霉素C的总剂量均根据体表面积确定，则腹腔内丝裂霉素C的药代动力学更一致。
为了为接受腹腔内热灌注丝裂霉素C的患者制定统一的治疗方案，应根据体表面积确定药物的总剂量和化疗溶液的总体积。如果化疗溶液的体积不是基于患者体表面积，则关于毒性的预测不太准确。
