      Document 0057
 DOCN  DRG0057
 UNIQUE IDENTIFIER        DRG-0190
 NAME OF SUBSTANCE        Paclitaxel [USAN 1996]
 REGISTRY NUMBER          33069-62-4
 SYNONYMS                 Taxol [USAN 1996]
 SYNONYMS                 Taxol A [Merck Index 1989]
 PROTOCOL ID NUMBERS      NCI 93 C-193
 SECONDARY SOURCE ID      NSC-125973 [USAN 1996]
 SECONDARY SOURCE ID      BMS-181339-01 [USAN 1996]
 PHARMACOLOGICAL ACTION   MODE OF ACTION: Promotes the assembly of
                          microtubules and inhibits the tubulin
                          disassembly process. Following IV doses,
                          paclitaxel plasma levels decline in a
                          biphasic manner. The initial rapid decline
                          represents distribution to the peripheral
                          compartment and elimination of the drug.
                          After IV doses of 15-275 mg/m2 as 1, 6 or 24
                          h infusions, mean values for cumulative
                          urinary recovery of unchanged drug ranged
                          from 1.3% to 12.6% of the dose, indicating
                          extensive nonrenal clearance. High drug
                          concentrations have been reported in the
                          bile. [PDR 1995]
 DISEASES STUDIED/TREATED Kaposi's sarcoma and HIV infection [AmFAR Tx
                          Dir 1995;7(4)]
 CLASSIFICATION CODE      Antineoplastic [USAN 1996]
 OTHER MAJOR USES         Breast cancer and metastatic carcinoma of the
                          ovary [PDR 1995]
 SUBSTANCE INTERACTIONS   Avoid concomitant therapy with bone marrow
                          depressants, live and killed virus vaccines,
                          and ketoconazole. The administration of
                          paclitaxel after, rather than before,
                          cisplatin increases myelosuppression. [USP DI
                          1995] [PDR 1995]
 ADVERSE EFFECTS          Adverse effects include neutropenia,
                          peripheral neuropathy, mucositis, alopecia,
                          N/V, diarrhea, cardiotoxicity, and
                          hypotension. [PDR 1995]
 CONTRAINDICATIONS        Contraindicated in patients who have a
                          history of hypersensitivity reactions to
                          paclitaxel. [PDR 1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: A diterpenoid taxane
                          isolated from the bark of the Pacific yew
                          tree [USP DI 1995]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C47H51NO14 [USAN 1996]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 853.92 [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   MELTING POINT: 213-216 C [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   ELEMENTAL COMPOSITION: C66.11% H6.02% N1.64%
                          O26.23% [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: Clear colorless to
                          slightly yellow viscous solution or white to
                          off-white crystalline powder [PDR 1995]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Intravenous infusion. [PDR
                          1995]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Single dose vials, 30 mg/5 ml.
                          [PDR 1995]
 SUBSTANCE DELIVERY DATA  STORAGE: Store at 2-8 C and protect from
                          light. [PDR 1995]
 REFERENCES               Sarris AH, Younes A, McLaughlin P, Moore D,
                          Hagemeister F, Swan F, Rodriguez MA,
                          Romaguera J, North L, Mansfield P, Callendar
                          D, Mesina O, Cabanillas F. Cyclosporin A does
                          not reverse clinical resistance to paclitaxel
                          in patients with relapsed non-Hodgkin's
                          lymphoma. J Clin Oncol. 1996 Jan;14(1):233-9.
 REFERENCES               Sweet MJ, Hume DA. RAW264 macrophages stably
                          transfected with an HIV-1 LTR reporter gene
                          provide a sensitive bioassay for analysis of
                          signalling pathways in macrophages stimulated
                          with lipopolysaccharide, TNF- alpha or taxol.
                          J Inflamm. 1995;45(2):126-35.
 REFERENCES               Saville MW, Lietzau J, Pluda JM, Feuerstein
                          I, Odom J, Wilson WH, Humphrey RW, Feigal E,
                          Steinberg SM, Broder S, et al. Treatment of
                          HIV-associated Kaposi's sarcoma with
                          paclitaxel. Lancet. 1995 Jul
                          1;346(8966):26-8.
 REFERENCES               Saville MW, Lietzau J, Pluda JM, Wilson W,
                          Bailey J, Cohen R, Feigal F, Feuerstein I,
                          Humphrey R, Broder S, et al. Use of
                          paclitaxel (Taxol(TM)) as therapy for
                          HIV-associated kaposi's sarcoma (KS). Natl
                          Conf Hum Retroviruses Relat Infect (2nd).
                          1995 Jan 29-Feb 2;:79.
 REFERENCES               Saville MW, Lietzau J, Pluda M, Wilson W,
                          Bailey J, Cohen R, Feigal E, Humphrey R,
                          Broder S, Yarchoan R. Phase II study of
                          paclitaxel (Taxol) for the treatment of
                          HIV-associated Kaposi's sarcoma (KS) (Meeting
                          abstract). Blood;84(10,Suppl 1):248a 1994.
 REFERENCES               Saville MW, Lietzau J, Wilson W, Pluda J,
                          Bailey J, Cohen R, Feigal E, Broder S,
                          Yarchoan R. A trial of Paclitaxel (TAXOL) in
                          patients with HIV-associated Kaposi's sarcoma
                          (KS) (Meeting abstract). Proc Annu Meet Am
                          Soc Clin Oncol. 1994;13:A20.
 REFERENCES               Hainsworth JD, Greco FA. Paclitaxel
                          administered by 1-hour infusion. Preliminary
                          results of a phase I/II trial comparing two
                          schedules. Cancer. 1994 Aug 15;74(4):1377-82.
 REFERENCES               Schiller JH, Storer B, Tutsch K, Arzoomanian
                          R, Alberti D, Feierabend C, Spriggs D. A
                          phase I trial of 3-hour infusions of
                          paclitaxel (Taxol) with or without
                          granulocyte colony-stimulating factor. Semin
                          Oncol. 1994 Oct;21(5 Suppl 8):9-14.
 REFERENCES               Greco FA, Hainsworth JD. Paclitaxel (Taxol):
                          phase I/II trial comparing 1-hour infusion
                          schedules. Semin Oncol. 1994 Oct;21(5 Suppl
                          8):3-8.
 REFERENCES               Gotaskie GE, Andreassi BF. Paclitaxel: a new
                          antimitotic chemotherapeutic agent. Cancer
                          Pract. 1994 Jan-Feb;2(1):27-33.
 ENTRY MONTH              9310
 LAST REVISION DATE       960417
 

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