Seventy intraperitoneal administrations of doxorubicin were performed in 12 patients with malignant disease in the abdominopelvic space. Peritoneal and hematologic drug levels were measured by fluorimetric assay. A first-order decline in the peritoneal level was determined (T1/2 96 ± 18 min), with a mean drug absorption of 84 % in 4 h (range 40-96 %) and a mean ratio of a peak dialysate/peak serum level of 111 (range 12-390). Gastrointestinal toxicity was common and peritoneal phlogosis occurred twice. The doxorubicin level and the time of peritoneal exposure seem to be critical factors for major local toxicity. At a moderate concentration doxorubicin can be intraperitoneally administered, but its usefullness is probably confined to patients with minimal abdominal disease.
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References
1.
BenjaminR.S., RiggsC.E., BachurN.R.: Plasma pharmacokinetics of adriamycin and its metabolites in humans with normal hepatic and renal function.Cancer Res., 37: 1416–1420, 1977.
2.
CasperE.S., KelsenD.P., AlcockN.W., LewisJ.L.: I.p. Cisplatin in patients with malignant ascites: pharmacokinetic evaluation and comparison with i.v.route. Cancer Treat. Rep., 67: 235–238, 1983.
3.
ChangP., RiggsC.E., ScheererM.T., WiernikP.H., BachurN R.: Combination chemotherapy with adriamycn and streptozotocin.Clin. Pharm. Ther., 20: 611–616, 1976.
4.
ClarksonB., O'ConnorA., WinstonL., HutchinsonD.: The physiologic disposition of 5-fluorouracil and 5-fluoro-2-deoxyuridine in man.Clin. Pharmacol. Ther., 5: 581–610, 1964.
5.
DedrickR.L., FlessnerM.F., CollinsJ.M., SchultzJ.S.: Is the peritoneum a membrane?ASAIO J., 5: 1–8, 1982.
6.
DedrickR.L., MyersC.E., BungayP.M., De VitaV.T.: Pharmacokinetic rationale for peritoneal drug administration in the treatment of ovarian cancer.Cancer Treat. Rep., 62: 1–13, 1978.
7.
DemicheliR., JirilloA., BonciarelliG., BelliniA., PetrosinoL., BigiL., GarusiG.F.: Pharmacological data and technical feasibility of intraperitoneal 5-fluorouracil administration.Tumori, 68: 437–441, 1982.
8.
GreenT.: Hemisulfur mustard in the palliation of patients with metastatic ovarian cancer.Obstet. Gynecol., 64: 383–393, 1959.
9.
JonesR.B., CollinsJ.M., MyersC.B., BrooksA.B., HubbardS.M., BalowJ.E., BrannanM.P., DedrickR.L., De VitaV.T.: High-volume intraperitoneal chemotherapy with methotrexate in patients with cancer.Cancer Res., 41: 55–59, 1981.
10.
KottmeierM.L.: Treatment of ovarian cancer with thiotepa.Obstet. Gynecol., 11: 428–438, 1968.
11.
LitterstC.L., CollinsJ.M., LoweM.C., ArnoldS.T., PowellD.M., GuarinoA.M.: Local and systemic toxicity resulting from large-volume i.p. administration of doxorubicin in the rat.Cancer Treat. Rep., 66: 157–161, 1982.
12.
MorganL.R., WeatherallT.J.: Pharmacology and drug distribution.Int. J. Radiat. Oncol. Biol. Phys., 5: 1205–1212, 1979.
13.
OzolsR.F., GershonY.L., DoroshowJ.H., Grot-zingerK.R., MyersC.E., FisherR.I., YoungR.C.: Chemotherapy for murine ovarian cancer: a rationale for i.p. therapy with adriamycin.Cancer Treat. Rep., 63: 269–273, 1979.
14.
OzolsR.F., YoungR.C., SpeyerJ.L., SugarbakerP.H., GreenR., JenkinsJ., MyersC.M.: Phase I and pharmacological studies of adriamycin administered intraperitoneally to patients with ovarian cancer.Cancer Res., 42: 4265–4269, 1982.
15.
PiazzaE., NataleN., TrabattoniA., MariscottiC., MoscaL., LibrettiA., OttolenghiA., MorascaL.: Plasma and tissue distribution of adriamycin in patients with pelvic cancer.Tumori, 67: 533–537, 1981.
16.
RobozJ., JacobsA.J., HollandJ.F., DeppeG., CoenC.J.: Intraperitoneal infusion of doxorubicin in the treatment of gynecological carcinomas.Med. Ped. Oncol., 9: 245–250, 1981.
17.
RossoR., RavazzoniC., EspositoM., SalaR., SantiL.: Plasma and urinary levels of adriamycin in man.Eur. J. Cancer, 8: 455–459, 1972.
18.
SpeyerJ.L., SugarbakerP.H., CollinsJ.M., DedrickR.L., KlekerR.W., MyersC.E.: Portal levels and hepatic clearance of 5-fluorouracil after intraperitoneal administration in tumors.Cancer Res., 41: 1916–1922, 1981.
