      Document 0062
 DOCN  DRG0062
 UNIQUE IDENTIFIER        DRG-0185
 NAME OF SUBSTANCE        Doxorubicin hydrochloride (liposomal) [AmFAR
                          Tx Dir 1995;7(4)]
 SYNONYMS                 DOX-SL [AIDS Treatment News]
 SYNONYMS                 DOXIL [J Clin Oncol 1995 Apr;13(4)]
 PROTOCOL ID NUMBERS      FDA 134A
 PROTOCOL ID NUMBERS      FDA 134B
 PROTOCOL ID NUMBERS      FDA 134C
 PROTOCOL ID NUMBERS      FDA 134D
 PROTOCOL ID NUMBERS      NIAID ACTG 286
 SECONDARY SOURCE ID      DRG
 PHARMACOLOGICAL ACTION   MODE OF ACTION: Liposomal doxorubicin may
                          cause regression of KS via 2 different
                          mechanisms: (1) by highly specific inhibition
                          of KS spindle cell proliferation and (2) by
                          induction of monocyte chemoattractant
                          protein-1 expression in KS spindle cells,
                          which may result in increased recruitment of
                          phagocytic cells into the lesions. Liposome
                          encapsulation may increase cellular uptake of
                          doxorubicin and reduce systemic toxicities.
                          Liposome encapsulation can markedly alter the
                          biodistribution and pharmacokinetics of well
                          known chemotherapeutic agents. [AmFAR Tx Dir
                          1995;7(4)] [J Acquir Immu Defic Syndr
                          1993;6(3)] [Res Virol 1994 May-Aug:145(3-4)]
 DISEASES STUDIED/TREATED Treatment of AIDS-related Kaposi's sarcoma
                          [AmFAR Tx Dir 1995;7(4)] [J Clin Oncol 1995
                          Apr;13(4)]
 DISEASES STUDIED/TREATED FDA approved 11/17/95 for the treatment of
                          Kaposi's sarcoma in AIDS patients with
                          disease that has progressed on prior
                          combination chemotherapy or in patients who
                          are intolerant to such therapy [FDA Bulletin]
 CLASSIFICATION CODE      Antineoplastic [AmFAR Tx Dir 1995;7(4)]
 ADVERSE EFFECTS          Side effects can include stomatitis, hair
                          loss, nausea, and hematological toxicity. One
                          case of fatal hepatic failure in a patient
                          with a history of symptom-free hepatitis B
                          was attributed to liposomal doxorubicin.
                          [AmFAR Tx Dir 1995;7(4)] [J Clin Oncol 1995
                          Apr;13(4)]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: An intravenous formulation
                          of doxorubicin that has been encapsulated in
                          liposomes [AmFAR Tx Dir 1995;7(4)]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: DOX-SL is supplied in vials as a
                          liquid. [FDA 134C]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Diluted in 250 ml of 5%
                          Dextrose Injection, USP and administered by
                          intravenous infusion over 30 minutes. [FDA
                          134C]
 MANUFACTURERS            Sequus Pharmaceutical Inc
 REFERENCES               Uziely B, Jeffers S, Isacson R, Kutsch K,
                          Wei-Tsao D, Yehoshua Z, Libson E, Muggia FM,
                          Gabizon A. Liposomal doxorubicin: antitumor
                          activity and unique toxicities during two
                          complementary phase I studies. J Clin Oncol
                          1995 Jul;13(7):1777-85.
 REFERENCES               Harrison M, Tomlinson D, Stewart S.
                          Liposomal-entrapped doxorubicin: an active
                          agent in AIDS-related Kaposi's  sarcoma. J
                          Clin Oncol. 1995 Apr;13(4):914-20.
 REFERENCES               Wagner D, Kern WV, Kern P. Liposomal
                          doxorubicin in AIDS-related Kaposi's sarcoma:
                          long-term experiences. Clin Investig 1994
                          Jun;72(6):417-23.
 REFERENCES               Sturzl M, Zietz C, Eisenburg B, Goebel FD,
                          Gillitzer R, Hofschneider PH, Bogner JR.
                          Liposomal doxorubicin in the treatment of
                          AIDS-associated Kaposi's sarcoma: clinical,
                          histological and cell biological evaluation.
                          Res Virol 1994 May-Aug;145(3-4):261-9.
 REFERENCES               Northfelt DW. Stealth liposomal doxorubicin
                          (SLD) delivers more doxorubicin (DOX) to
                          AIDS-Kaposi's sarcoma (AIDS-KS) lesions than
                          to normal skin (Meeting abstract). Proc Annu
                          Meet Am Soc Clin Oncol. 1994;13:A5.
 REFERENCES               Bogner JR, Kronawitter U, Rolinski B,
                          Truebenbach K, Goebel FD. Liposomal
                          doxorubicin in the treatment of advanced
                          AIDS-related Kaposi sarcoma. J Acquir Immune
                          Defic Syndr. 1994 May;7(5):463-8.
 REFERENCES               Law TM, Mencel P, Motzer RJ. Phase II trial
                          of liposomal encapsulated doxorubicin in
                          patients with advanced renal cell carcinoma.
                          Invest New Drugs 1994;12(4):323-5.
 REFERENCES               Gabizon A, Isacson R, Libson E, Kaufman B,
                          Uziely B, Catane R, Ben-Dor CG, Rabello E,
                          Cass Y, Peretz T, et al. Clinical studies of
                          liposome-encapsulated doxorubicin. Acta
                          Oncol; VOL 33, ISS 7, 1994, P779-86.
 REFERENCES               Simpson JK, Miller RF, Spittle MF. Liposomal
                          doxorubicin for treatment of AIDS-related
                          Kaposi's sarcoma. Clin Oncol (R Coll Radiol);
                          VOL 5, ISS 6, 1993, P372-4.
 REFERENCES               Conley BA, Egorin MJ, Whitacre MY, Carter DC,
                          Zuhowski EG, Van Echo DA. Phase I and
                          pharmacokinetic trial of
                          liposome-encapsulated doxorubicin. Cancer
                          Chemother Pharmacol 1993;33(2):107-12.
 ENTRY MONTH              9307
 LAST REVISION DATE       960417
 

SOURCE: National Library of Medicine, Bethesda, MD.  Distributed by AEGIS.
