Phase II Trial of Topotecan and Cisplatin in Persistent or Recurrent Squamous and Nonsquamous Carcinomas of the Cervix

Fiorica, James V.; Holloway, Robert; Ndubisi, Boniface; Orr, James W.; Grendys, Edward C.; Boothby, Richard A.; DeCesare, Steven; LaPolla, James P.; Hoffman, Michael L; Patel, Jyoti D.

doi:10.1006/gyno.2001.6557

Cited by 63 publications

(31 citation statements)

References 21 publications

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“…Fiorica et al [44] evaluated topotecan and cisplatin in the phase II setting in women with both squamous and non-squamous cell carcinomas of the cervix. Unlike the 5-day infusion schedules employed by the GOG in protocols 76U and 127F, to balance the added toxicity of cisplatin, the dose of topotecan was decreased from 1.5 mg/m 2 to 0.75 mg/m 2 and administered over 3 days.…”

Section: The 76 Series and Other Phase II Studiesmentioning

confidence: 99%

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Gynecologic oncology group trials of chemotherapy for metastatic and recurrent cervical cancer

Tewari

Monk

2005

Curr Oncol Rep

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Section: The 76 Series and Other Phase II Studiesmentioning

confidence: 99%

“…The papers by Fiorica et al [44], Buxton et al [45], and Long et al [46], together with the GOG-76 trials [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31], laid the foundation for the phase III GOG experience in metastatic cervical carcinoma.…”

Section: The 76 Series and Other Phase II Studiesmentioning

confidence: 99%

Gynecologic oncology group trials of chemotherapy for metastatic and recurrent cervical cancer

Tewari

Monk

2005

Curr Oncol Rep

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“…Topotecan combinations might also be investigated in diseases that are historically resistant to chemotherapy. Fiorica et al (2002) reported a 28% (nine of 32) overall response rate for topotecan/cisplatin in patients with recurrent cervical cancer.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, an oral formulation of topotecan has also been investigated in SCLC ) and ovarian cancer (Clarke-Pearson et al, 2001). Preliminary reports indicate that topotecan also has activity in non-small-cell lung cancer (NSCLC) (Lynch et al, 1994;PerezSoler et al, 1996), cervical cancer (Fiorica et al, 2002), and haematologic malignancies (Beran et al, 1998). Additional studies are required to determine the activity of topotecan in other cancers.…”

mentioning

confidence: 99%

“…The predictable toxicity profile of topotecan makes it feasible to combine topotecan with other agents with nonoverlapping toxicities. Topotecan has been investigated in doublet and triplet combinations with several agents, including cisplatin, paclitaxel, and etoposide (Ardizzoni et al, 1999;Frasci et al, 1999;Hainsworth et al, 1999;Jacobs et al, 1999;O'Neill et al, 2001;Fiorica et al, 2002). Randomised trials are underway in several diseases to evaluate the efficacy of topotecan in combination with other agents.…”

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Ex vivo analysis of topotecan: advancing the application of laboratory-based clinical therapeutics

et al. 2003

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Topotecan is currently approved for relapsed small-cell lung cancer and ovarian cancer. Topotecan's efficacy in the second-line setting and novel mechanism of action suggest broad antitumour activity. We utilised a clinically validated, cell-death, ex vivo assay in human tumour explants to examine the activity profile of topotecan alone and in combination with other antitumour agents. Serial dilutions of topotecan alone and in combination with other cytotoxic agents were applied to biopsy specimens of non-small-cell lung cancer (NSCLC) and breast, colon, and prostate cancers. Dose -response curves were interpolated to provide 50% lethal concentrations (LC 50 ). The degree of synergy (by median effect) and normalised Z-scores (raw scores converted to relative activity distributed around the mean) were then computed. Single-agent activity was observed for topotecan in all four tumour types. In 57 chemotherapy-naive specimens, NSCLC revealed the highest activity, demonstrated by the lowest LC 50 value (0.2670.06 mg ml À1 ; P ¼ 0.002). Overall, previously treated and chemotherapy-naive specimens revealed no significant differences in mean LC 50 's. Synergy was observed for several combinations, including topotecan plus cisplatin in prostate and for topotecan plus 5-fluorouracil in breast cancers. The Z-score analyses conducted suggest activity for previously unexplored drug regimens, including topotecan plus 5-fluorouracil, vinorelbine, and mitomycin-C in NSCLC and breast cancer. Phase II studies are underway to determine the degree to which these ex vivo findings will translate into improved clinical results. Topotecan, a semisynthetic, water-soluble derivative of camptothecin, is an inhibitor of topoisomerase I (Kingsbury et al, 1991). This derivative is more stable, has increased solubility, a shorter half-life, and decreased toxicity compared with its parent compound (Verweij et al, 1993;Burke and Mi, 1994;Rothenberg, 1997). Topoisomerase I is a nuclear enzyme that relieves torsional strain on supercoiled DNA and creates single-strand breaks during DNA replication. Topotecan prevents topoisomerase I from repairing the cleaved DNA, which results in double-stranded DNA breaks and eventually apoptosis. The unique mechanism of action of topotecan and lack of clinical crossresistance with other antineoplastic compounds suggest that topotecan has the potential for broad antitumour activity.The activity of topotecan has been demonstrated in several open-label, randomised phase II and III trials. Currently, topotecan is approved for the treatment of relapsed small-cell lung cancer (SCLC) (Eckardt et

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Innovations in the treatment of invasive cervical cancer

Stehman¹,

Rose²,

Greer³

et al. 2003

Cancer

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Phase II Trial of Topotecan and Cisplatin in Persistent or Recurrent Squamous and Nonsquamous Carcinomas of the Cervix

Cited by 63 publications

References 21 publications

Gynecologic oncology group trials of chemotherapy for metastatic and recurrent cervical cancer

Gynecologic oncology group trials of chemotherapy for metastatic and recurrent cervical cancer

Ex vivo analysis of topotecan: advancing the application of laboratory-based clinical therapeutics

Innovations in the treatment of invasive cervical cancer

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