To review the pharmacologic, pharmacokinetic, therapeutic, and safety aspects of topotecan, a new antineoplastic agent, and to assess its role in the treatment of cancer.
DATA SOURCES:
MEDLINE database English language only, January 1990–March 1998; SmithKline Beecham Pharmaceuticals; published articles, books, and abstracts.
STUDY SELECTION:
Studies in humans with cancer, clinical case reports, open clinical trials, and controlled clinical studies. Efficacy studies were limited primarily to trials with at least 20 evaluable patients.
DATA EXTRACTION:
Relevant data were extracted only from published reports. Data were obtained from studies in both articles and abstracts. Only articles written in English were reviewed.
DATA SYNTHESIS:
Topotecan is an effective second- or third-line therapy for patients with advanced ovarian cancer and is comparable to ifosfamide, liposomal doxorubicin, and paclitaxel. Activity in combination with other agents and as a first-line agent is yet to be determined. Limited data indicate activity in small-cell lung cancer, cancers of the breast and uterus, and in nonlymphocytic leukemia. The dose-limiting toxicity is myelosuppression.
CONCLUSIONS:
Topotecan is an effective second-line agent for patients with unresponsive or relapsed cancer of the ovary. It appears to be similar to other active agents in patients with this disease status. Its ultimate role in ovarian cancer and other neoplasms awaits additional evaluation in combination with other agents and as first-line therapy.
RivoryLPRobertJ. Molecular, cellular, and clinical aspects of the pharmacology of 20 (S)-camptothecin and its derivatives. Pharmacol Ther1995;68: 269–96.
3.
HerbenVMMten Bokkel HuininkWWBeijnenJH. Clinical pharmacokinetics of topotecan. Clin Pharmacokinet1996;31: 85–102.
4.
SaltzLSirottMYoungCTongWNiedzwieckiDTzy-JyunYPhase I clinical and pharmacology study of topotecan given daily for 5 consecutive days to patients with advanced solid tumors, with attempt at dose intensification using recombinant GCSF. J Natl Cancer Inst1993;85:1499–1507.
5.
GrochowLBRowinskyEKJohnsonRLudemanSKaufmannSHMcCabeFLPharmacokinetics and pharmacodynamics of topotecan in patients with advanced cancer. Drug Metab Dispos1992;20:706–13.
6.
VerweijJLundBBeijnenJPlantingAde-Boer-DennertMKoierIPhase I and pharmacokinetic study of topotecan: A new topoisomerase inhibitor. Ann Oncol1993;4:673–8.
7.
RowinskyEKGrochowLBHendricksCBEttingerDSForastiereAAHurowitzLAPhase I and pharmacokinetic study of topotecan: A novel topoisomerase I inhibitor. J Clin Oncol1992;10:647–56.
8.
van WarmerdamLJCVerweijJSchellensJHMRosingHDaviesBEde-Boer-DennertMPharmacokinetics and pharmacodynamics of topotecan administered daily for 5 days every 3 weeks. Cancer Chemother Pharmacol1995;35:237–45.
9.
BlaneySMBalisFMColeDECraigCReidJMAmerMMPediatric Phase I trial and pharmacokinetic studies of topotecan administered as a 24-hour continuous infusion. Cancer Res1993;53:1032–6.
10.
van WarmerdamLJCten Bokkel HuininkWWRodenhuisSKoierIDaviesBERosingHPhase I clinical and pharmacokinetic study of topotecan administered by a 24-hour continuous infusion. J Clin Oncol1995;13:1768–76.
11.
BakerSDHeidmanRLCromWRKutteschJFGajjarAStewartCF. Cerebrospinal fluid pharmacokinetics and penetration of continuous infusion topotecan in children with central nervous system tumors. Cancer Chemother Pharmacol1996;37: 195–202.
12.
KuhnJBurrisSIrvinRWallRRodriguezGWeissGPharmacokinetics of topotecan following a 30 minute or 3 day continuous infusion (abstract). Ann Oncol1992;3 (suppl 1):83.
13.
StewartCFBakerSDHeidmanRLJonesDCromWRPrattCBClinical pharmacokinetics of continuous infusion topotecan in children: Systemic exposure predicts hematologic toxicity. J Clin Oncol1994;12:1946–54.
14.
O'ReillySRowinskyESlichenmyerWDonehowerRCForastiereAEttingerDPhase I and pharmacologic studies of topotecan in patients with impaired hepatic function. J Natl Cancer Inst1996;88:817–24.
15.
O'ReillySRowinskyEKSlichenmyerWDonehowerRCForastiereAAEttingerDSPhase I and pharmacologic study of topotecan in patients with impaired renal function. J Clin Oncol1996;14:3062–73.
16.
CreemersGJSchellensJHMBeijnenJHPlantingASThRosingHde-Boer-DennertMELBioavailability of oral topotecan, a new topoisomerase I inhibitor (abstract). Proc Am Soc Clin Oncol1994;13:132.
17.
KuhnJRizzoJEckardtJFieldsSCobbPRodriguezGPhase I bioavailability study of oral topotecan (abstract). Proc Am Soc Clin Oncol1995;14:474.
18.
CreemersGJGerritsCJHEckardtJRSchellensJHMBurrisHAPlantingASTPhase I and pharmacologic study of oral topotecan administered twice daily for 21 days to adult patients with solid tumors. J Clin Oncol1997;15:1087–93.
LandisSHMurrayTBoldenSWingoPA. Cancer statistics 1998. CA Cancer J Clin1998;48: 6–29.
21.
YoungRCPerezCAHoskinsWJ. Cancer of the ovary. In: DeVitaVTJrHellmanSRosenbergSA, eds. Cancer principles and practice of oncology. 4th ed.Philadelphia, PA: JB Lippincott Co., 1993: 1226–63.
22.
McGuireWPHoskinsWJBradyMFKuceraPRPartridgeEELookKYCyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer. N Engl J Med1996;334:1–6.
23.
BookmanMAMcGuireWPIIIKilpatrickDKeenanEHoganWMJohnsonSWCarboplatin and paclitaxel in ovarian carcinoma: A Phase I study of the gynecologic oncology group. J Clin Oncol1996;14:1895–902.
24.
VergoteIHimmelmannAFrankendalBScheistroenMVlachosKTropeC. Hexamethylmelamine as second-line therapy in platin-resistant ovarian cancer. Gynecol Oncol1992;47: 282–6.
25.
MooreDHValeaFCrumplerLSFowlerWCJr. Hexamethylmelamine/altretamine as second-line therapy for epithelial ovarian carcinoma. Gynecol Oncol1993;51: 109–12.
26.
PiccartMJGoreMten Bokkel HuininkWvan OostromAVerweijJWandersJDocetaxel: An active new drug for treatment of advanced epithelial ovarian cancer. J Natl Cancer Inst1995;87:676–81.
27.
HoskinsPJSwenertonKD. Oral etoposide is active against platinum-resistant epithelial ovarian cancer. J Clin Oncol1994;12: 60–3.
28.
RosePGBlessingJAMayerARHomesleyHD. Prolonged oral etoposide as second-line therapy for platinum-resistant and platinum-sensitive ovarian carcinoma: A gynecologic oncology group study. J Clin Oncol1998;16: 405–10.
29.
LundBHansenOPNeijtJPTheiladeKHansenM. Phase II study of gemcitabine in previously platinum-treated ovarian cancer patients. Anti-cancer Drugs1995;6 (suppl 6): 61–2.
30.
MarkmanMHakesTReichmanBLewisJLJrRubinSJonesWIfosfamide and mesna in previously treated advanced epithelial ovarian cancer: Activity in platinum-resistant disease. J Clin Oncol1992;10:243–8.
31.
MuggiaFMHainsworthJDJeffersSMillerPGroshenSTanMPhase II study of liposomal doxorubicin in refractory ovarian cancer: Antitumor activity and toxicity modification by liposomal encapsulation. J Clin Oncol1997;15:987–93.
32.
HatchKDBeechamJBBlessingJACreasmanWT. Responsiveness of patients with advanced ovarian carcinoma to tamoxifen. Cancer1991;68: 269–71.
33.
MarkmanMIsemingerKAHatchKDCreasmanWTBarnesWDubeshterB. Tamoxifen in platinum-refractory ovarian cancer: A Gynecologic Oncology Group ancillary report. Gynecol Oncol1996;62: 4–6.
34.
ArmstrongDRowinskyEDonehowerRRosensheinNWalczakJMcGuireW. A Phase II trial of topotecan as salvage therapy in epithelial ovarian cancer (abstract). Proc Am Soc Clin Oncol1995;14:275.
35.
GordonABookmanMMalmstromHBolisGMangioniCHallJEfficacy of topotecan in advanced epithelial ovarian cancer after failure of platinum and paclitaxel: International topotecan study group trial (abstract). Proc Am Soc Clin Oncol1996;15:282.
36.
MalmstromHSorbeBSimonsenEE. The effect of topotecan in platinum refractory ovarian cancer (abstract). Proc Am Soc Clin Oncol1996;15:299.
37.
KudelkaAPTresukosolDEdwardsCLFreedmanRSLevenbackCChantarawirojPPhase II study of intravenous topotecan as a 5-day infusion for refractory epithelial ovarian carcinoma. J Clin Oncol1996;14:1552–7.
38.
CreemersGJBolisGGoreMScartoneGLacaveAJGuastallaJPTopotecan, as active drug in the second-line treatment of epithelial ovarian cancer: Results of a large European Phase II study. J Clin Oncol1996;14:3056–61.
39.
HochsterHSpeyerJWadlerSRunowiczCWallachROratzRPhase II study of topotecan (TPT) 21-day infusion in platinum-treated ovarian cancer: A highly active regimen (A NYGOG study) (abstract). Proc Am Soc Clin Oncol1996;15:285.
40.
ten Bokkel HuininkWGoreMCarmichaelJGordonAMalfetanoJHudsonITopotecan versus paclitaxel for the treatment of recurrent epithelial ovarian cancer. J Clin Oncol1997;15:2183–93.
41.
IhdeDCPassHIGlatsteinE. Small cell lung cancer. In: DeVitaVTJrHellmanSRosenbergSA, eds. Cancer principles and practice of oncology. 5th ed.Philadelphia, PA: Lippincott-Raven, 1997: 911–49.
42.
SchillerJHKimKMHutsonPDeVoreRGlickJStewartJPhase II study of topotecan in patients with extensive stage small-cell carcinoma of the lung: An Eastern Cooperative Oncology Group trial. J Clin Oncol1996;14:2345–52.
43.
Perez-SolerRGlissonBSLeeJSFossellaFVMurphyWKShinDMTreatment of patients with small-cell lung cancer refractory to etoposide and cisplatin with the topoisomerase I poison topotecan. J Clin Oncol1996;14:2785–90.
44.
ArdizzoniAHansenHDombernowskyPGamucciTKaplanSPostmusPTopotecan, a new active drug in the second-line treatment of small-cell lung cancer: A Phase II study in patients with refractory and sensitive disease. J Clin Oncol1997;15:2090–6.
45.
EckardtJGrallaRPalmerMCGandaraDLapianoJSanderATopotecan (T) as second-line therapy in patients (pts) with small cell lung cancer (SCLC): A Phase II study (abstract). European Society for Medical Oncology 21st congress: Vienna, Austria, 1966, Ann Oncol1996;7 (suppl 5):513P.
46.
WeitzJJJungS-HMarschkeRFJrFitchTRJettJR. Randomized Phase II trial of two schedules of topotecan for the treatment of advanced stage non-small cell lung carcinoma (NSCLC): A North Central Cancer Treatment Group trial (abstract). Proc Am Soc Clin Oncol1995;14:348.
47.
LynchTJJrKalishLStraussGEliasASkarinAShulmanLNPhase II study of topotecan in metastatic non-small cell lung cancer. J Clin Oncol1994;12:347–52.
48.
Perez-SolerRFossellaFVGlissonBSLeeJSMurphyWKShinDMPhase II study of topotecan in patients with advanced non-small cell lung cancer previously untreated with chemotherapy. J Clin Oncol1996;14:503–13.
49.
KindlerHLKrisMGSmithIESlevinMLKrebsJB. Continuous infusion topotecan as first-line therapy in patients with non-small cell lung cancer (NSCLC): A Phase II study (abstract). Proc Am Soc Clin Oncol1997;16:472a.
50.
Perez-SolerRKhuriFPistersKMRobinsonRWimberlyALeeJKPhase I study of topotecan in patients with squamous carcinoma of the lung previously untreated with chemotherapy (abstract). Proc Am Soc Clin Oncol1997;16:450a.
51.
O'ReillySDonehowerRCRowinskyEKOrdSGrochowLB. A Phase II trial of topotecan in patients with previously untreated pancreatic cancer. Anticancer Drugs1996;7: 410–4.
52.
ScherRMKosierowskiRLuschCAlexanderRFoxSRedeiIPhase II trial of topotecan in advanced or metastatic adenocarcinoma of the pancreas. Invest New Drugs1996;13:347–54.
53.
RobertFSoongSJWheelerRH. A Phase II study of topotecan in patients with recurrent head and neck cancer. Identification of an active new agent. Am J Clin Oncol1997;20: 298–302.
54.
SmithRELewDRodriguezGITaylorSASchullerDEnsleyJF. Evaluation of topotecan in patients with recurrent metastatic squamous cell carcinoma of the head and neck. A Phase II Southwest Oncology Group study. Invest New Drugs1996;14: 403–7.
55.
HudesGRKosierowskiRGreenbergR. Phase II study of topotecan in metastatic hormone-refractory prostate cancer. Invest New Drugs1995;13: 235–40.
56.
GiantonioBJKosierowskiRRamseyHEFoxSCMcAleerCARoethkeSPhase II study of topotecan (TT) for hormone-refractory prostate cancer (HRPC) (abstract). Proc Am Assoc Clin Oncol1993;12:247.
57.
LawTMIlsonDHMotzerRJ. Phase II trial of topotecan in patients with advanced renal cell carcinoma. Invest New Drugs1994;12: 143–5.
58.
KrautEHStaubusAMayernickDKingGBalcerzakSP. Phase II trial of topotecan in metastatic malignant melanoma (abstract). Proc Am Assoc Cancer Res1995;36:238.
59.
CreemersGJWandersJGamucciTVallentinSDirixLYSchoffskiPTopotecan in colorectal cancer: A Phase II study of the EORTC early clinical trials group. Ann Oncol1995;6:844–6.
60.
CreemersGJGerritsCJHSchellensJHMPlantingASTvan der BurgMELvan BeurdenVMPhase II and pharmacologic study of topotecan administered as a 21-day continuous infusion to patients with colorectal cancer. J Clin Oncol1996;14:2540–5.
61.
SugarmanSMAjaniJADaughertyKWinnRLanzottiVBeardenJDA Phase II trial of topotecan (TPT) for the treatment of advanced measurable colorectal cancer (abstract). Proc Am Assoc Clin Oncol1994;13:224.
62.
MacdonaldDCairncrossGStewartDForsythPSawkaCWainmanNPhase II study of topotecan in patients with recurrent malignant glioma. Ann Oncol1996;7:205–7.
63.
BurchPANovotonyPJBernathAMCascinoTLAddoFKKeppenMDA North Central Cancer Treatment Group Phase II trial of topotecan in relapsed gliomas (abstract). Proc Am Assoc Cancer Res1996;37:169.
64.
BlaneySMPhillipsPCPackerRJHeidemanRLBergSLAdamsonPCPhase II evaluation of topotecan for pediatric central nervous system tumors. Cancer1996;78:527–31.
65.
MaksymiukAWJungS-HMarschkeRFJrNairSJettJR. Phase II trial of topotecan in pleural mesothelioma: North Central Cancer Treatment Group (NCCTG) trial (abstract). Proc Am Soc Clin Oncol1995;14:435.
66.
BramwellVHCEisenhauerEABlacksteinMBoosGKnowlingMJolivetJPhase II study of topotecan (NSC 609 699) in patients with recurrent or metastatic soft tissue sarcoma. Ann Oncol1995;6:847–9.
67.
NodaKSasakiHYamamotoKYamamotoTNishimuraRSugiyamaTPhase II trial of topotecan for cervical cancer of the uterus (abstract). Proc Am Soc Clin Oncol1996;15:280.
68.
ChangAYGarrowGBorosLAsburyRPandyaKKengP. Clinical and laboratory studies of topotecan in breast cancer (abstract). Proc Am Soc Clin Oncol1995;14:105.
69.
GoldschmidtEBionneterraJFumoleauPOberlingFCupissofDMissetLA Phase II study of topotecan on a daily x 5 schedule as second-line single agent therapy in patients with advanced breast cancer (abstract). Proc Am Soc Clin Oncol1997;16:170a.
70.
BeranMKantarjianHO'BrienSKollerCAl-BitarMArbuckSTopotecan, a topoisomerase I inhibitor, is active in the treatment of myelodysplastic syndrome and chronic myelomonocytic leukemia. Blood1996;88:2473–9.
71.
PretiHAPlunkettWSarrisAHYounesAHagemeisterERodriguezMAPreliminary results of a Phase II trial of topotecan in patients with relapsing lymphoma (abstract). Blood1995;86:820a.
72.
ArbuckSGBlaylockBAChristianMCParkinsonDRTakimotoCH. The camptothecin topoisomerase I inhibitors. An update. In: KhayatDHortobagyiGN, eds. Progress in anti-cancer chemotherapy. Oxford, England: Blackwell Science Ltd., 1997: 3–27.
73.
ViettiTCristWRubyERaneyBRuymannFLinkMTopotecan window in patients with rhabdomyosarcoma. (RMS): An IRSG study (abstract). Proc Am Soc Clin Oncol1997;16:510a.
74.
KretschmarCKletzelMMurrayKJoshiVSmithEPaoPVUp front Phase II therapy with Taxol (TXL) and topotecan (Topo) in untreated children (>365 days) with disseminated (INSS stage 4) neuro-blastoma (NB) (abstract). Med Pediatr Oncol1995;25:243.
75.
KrautEHCrowleyJJWadeJLLaufmanLRAlsinaATaylorSAEvaluation of topotecan in resistant and relapsing multiple myeloma: A Southwest Oncology Group study. J Clin Oncol1998;16:589–92.
76.
RowinskyEKKaufmannSH. Topotecan in combination chemotherapy. Semin Oncol1997;24 (suppl 20):S20–6.
77.
SeiterKFeldmanEHalickaDTraganosFDarzynkiewiczZLakeDPhase I clinical and laboratory evaluation of topotecan and cytarabine in patients with acute leukemia. J Clin Oncol1997;15:44–51.
78.
CrumpMLiptonJHedleyDWStewartAKSuttonDKeatingAA Phase I trial of sequential topotecan and etoposide in adult acute myeloid leukemia (AML) (abstract). Blood1996;88 (suppl 1):867.
79.
RowinskyEKKaufmannSHGrochowLBBakerSDChenTLPeereboomDSequences of topotecan and cisplatin: Phase I, pharmacologic and in vitro studies examining sequence-dependence. J Clin Oncol1996;14:3074–84.
80.
AnzaiHFrostPAbbruzzeseJL. Synergistic cytotoxicity with combined inhibition of topoisomerase (Topo) I and II (abstract). Proc Am Assoc Cancer Res1992;33:431.
81.
KaufmannSHPeereboomDBuckwalterCASvingenPAGrochowLBDonehowerRCCytotoxic effects of topotecan combined with various anticancer agents in human cancer cell lines. J Natl Cancer Inst1996;88:734–41.
82.
KaufmannSH. Antagonism between camptothecin and topoisomerase II-directed chemotherapeutic agents in a human leukemia cell line. Cancer Res1991;51: 1129–36.
83.
EckardtJRBurrisHAVon HoffDDRodriquezGIFieldsSMRothenbergMLMeasurement of tumor topoisomerase I and II levels during the sequential administration of topotecan and etoposide (abstract). Proc Am Soc Clin Oncol1994;13:141.
84.
CooperBWLazarusHMCregerRWillsonJKVHoppelCLBergerSJA Phase I and pharmacodynamic study of sequential topotecan and etoposide (TE) in adult patients with refractory relapsed acute leukemia (RAL) (abstract). Proc Am Soc Clin Oncol1996;15:486.
85.
1997 Drug topics red book. Montvale, NJ: Medical Economics Co., 1997.
