A phase I study of TNP-470 administered to patients with advanced squamous cell cancer of the cervix

Andrzej P. Kudelka, Tally Levy, Claire F. Verschraegen, Creighton L. Edwards, Surintip Piamsomboon, Wichai Termrungruanglert, Ralph S. Freedman, Alan L. Kaplan, Dirk G. Kieback, Christina A. Meyers, Kurt Jaeckle, Evelyne Loyer, Melissa Steger, Rosario Mante, Giora Mavligit, Anthony Killian, Rosa A. Tang, Jordon U. Gutterman, John J. Kavanagh

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Abstract

A Phase I study of the novel angiongenesis inhibitor TNP-470 was performed. Patients with inoperable recurring or metastatic squamous cell cancer of the cervix with evaluable disease, no coagulopathy, and adequate renal, hepatic, and hematological function were eligible. One course of treatment consisted of an i.v. infusion of TNP-470 over 60 min every other day for 28 days, followed by a 14-day rest period. The starting dose was 9.3 mg/m2. Eighteen evaluable patients were treated, with a median age of 48 years (range 27-55) and performance status Zubrod 1 (range 0-2). Grade 3 neurotoxicities consisting of weakness, nystagmus, diplopia, and ataxia were encountered in two patients receiving the 71.2 mg/m2 dose. An intermediate dose level of 60 mg/m2 was evaluated and found to be well tolerated by three patients. Only one patient experienced grade 3 nausea on the 60 mg/m2 dose level. No myelosuppression, retinal hemorrhage, weight loss, or significant alopecia were observed. One patient had a complete response, which continues for 26 months, and three patients with initially progressive disease stage had stable disease for 5, 7.7, and 19+ months. Other Phase I studies, including over 200 patients, were performed concurrently with this study. Based on this experience, the dose of TNP- 470 recommended for further studies is 60 mg/m2 as a 60-min i.v. infusion every Monday, Wednesday, and Friday. Neurotoxicity was dose limiting, but appears to be reversible. Otherwise, the treatment was well tolerated. The drug may be active in squamous cell cancer of the cervix. Further studies of TNP-470 in squamous cell cancer of the cervix are warranted.

Original languageEnglish (US)
Pages (from-to)1501-1505
Number of pages5
JournalClinical Cancer Research
Volume3
Issue number9
StatePublished - Sep 1 1997

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Squamous Cell Neoplasms
Uterine Cervical Neoplasms
Retinal Hemorrhage
Diplopia
O-(chloroacetylcarbamoyl)fumagillol
Alopecia
Ataxia
Nausea
Weight Loss
Kidney
Liver
Therapeutics

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Kudelka, A. P., Levy, T., Verschraegen, C. F., Edwards, C. L., Piamsomboon, S., Termrungruanglert, W., ... Kavanagh, J. J. (1997). A phase I study of TNP-470 administered to patients with advanced squamous cell cancer of the cervix. Clinical Cancer Research, 3(9), 1501-1505.
Kudelka, Andrzej P. ; Levy, Tally ; Verschraegen, Claire F. ; Edwards, Creighton L. ; Piamsomboon, Surintip ; Termrungruanglert, Wichai ; Freedman, Ralph S. ; Kaplan, Alan L. ; Kieback, Dirk G. ; Meyers, Christina A. ; Jaeckle, Kurt ; Loyer, Evelyne ; Steger, Melissa ; Mante, Rosario ; Mavligit, Giora ; Killian, Anthony ; Tang, Rosa A. ; Gutterman, Jordon U. ; Kavanagh, John J. / A phase I study of TNP-470 administered to patients with advanced squamous cell cancer of the cervix. In: Clinical Cancer Research. 1997 ; Vol. 3, No. 9. pp. 1501-1505.
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abstract = "A Phase I study of the novel angiongenesis inhibitor TNP-470 was performed. Patients with inoperable recurring or metastatic squamous cell cancer of the cervix with evaluable disease, no coagulopathy, and adequate renal, hepatic, and hematological function were eligible. One course of treatment consisted of an i.v. infusion of TNP-470 over 60 min every other day for 28 days, followed by a 14-day rest period. The starting dose was 9.3 mg/m2. Eighteen evaluable patients were treated, with a median age of 48 years (range 27-55) and performance status Zubrod 1 (range 0-2). Grade 3 neurotoxicities consisting of weakness, nystagmus, diplopia, and ataxia were encountered in two patients receiving the 71.2 mg/m2 dose. An intermediate dose level of 60 mg/m2 was evaluated and found to be well tolerated by three patients. Only one patient experienced grade 3 nausea on the 60 mg/m2 dose level. No myelosuppression, retinal hemorrhage, weight loss, or significant alopecia were observed. One patient had a complete response, which continues for 26 months, and three patients with initially progressive disease stage had stable disease for 5, 7.7, and 19+ months. Other Phase I studies, including over 200 patients, were performed concurrently with this study. Based on this experience, the dose of TNP- 470 recommended for further studies is 60 mg/m2 as a 60-min i.v. infusion every Monday, Wednesday, and Friday. Neurotoxicity was dose limiting, but appears to be reversible. Otherwise, the treatment was well tolerated. The drug may be active in squamous cell cancer of the cervix. Further studies of TNP-470 in squamous cell cancer of the cervix are warranted.",
author = "Kudelka, {Andrzej P.} and Tally Levy and Verschraegen, {Claire F.} and Edwards, {Creighton L.} and Surintip Piamsomboon and Wichai Termrungruanglert and Freedman, {Ralph S.} and Kaplan, {Alan L.} and Kieback, {Dirk G.} and Meyers, {Christina A.} and Kurt Jaeckle and Evelyne Loyer and Melissa Steger and Rosario Mante and Giora Mavligit and Anthony Killian and Tang, {Rosa A.} and Gutterman, {Jordon U.} and Kavanagh, {John J.}",
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Kudelka, AP, Levy, T, Verschraegen, CF, Edwards, CL, Piamsomboon, S, Termrungruanglert, W, Freedman, RS, Kaplan, AL, Kieback, DG, Meyers, CA, Jaeckle, K, Loyer, E, Steger, M, Mante, R, Mavligit, G, Killian, A, Tang, RA, Gutterman, JU & Kavanagh, JJ 1997, 'A phase I study of TNP-470 administered to patients with advanced squamous cell cancer of the cervix', Clinical Cancer Research, vol. 3, no. 9, pp. 1501-1505.

A phase I study of TNP-470 administered to patients with advanced squamous cell cancer of the cervix. / Kudelka, Andrzej P.; Levy, Tally; Verschraegen, Claire F.; Edwards, Creighton L.; Piamsomboon, Surintip; Termrungruanglert, Wichai; Freedman, Ralph S.; Kaplan, Alan L.; Kieback, Dirk G.; Meyers, Christina A.; Jaeckle, Kurt; Loyer, Evelyne; Steger, Melissa; Mante, Rosario; Mavligit, Giora; Killian, Anthony; Tang, Rosa A.; Gutterman, Jordon U.; Kavanagh, John J.

In: Clinical Cancer Research, Vol. 3, No. 9, 01.09.1997, p. 1501-1505.

Research output: Contribution to journalArticle

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T1 - A phase I study of TNP-470 administered to patients with advanced squamous cell cancer of the cervix

AU - Kudelka, Andrzej P.

AU - Levy, Tally

AU - Verschraegen, Claire F.

AU - Edwards, Creighton L.

AU - Piamsomboon, Surintip

AU - Termrungruanglert, Wichai

AU - Freedman, Ralph S.

AU - Kaplan, Alan L.

AU - Kieback, Dirk G.

AU - Meyers, Christina A.

AU - Jaeckle, Kurt

AU - Loyer, Evelyne

AU - Steger, Melissa

AU - Mante, Rosario

AU - Mavligit, Giora

AU - Killian, Anthony

AU - Tang, Rosa A.

AU - Gutterman, Jordon U.

AU - Kavanagh, John J.

PY - 1997/9/1

Y1 - 1997/9/1

N2 - A Phase I study of the novel angiongenesis inhibitor TNP-470 was performed. Patients with inoperable recurring or metastatic squamous cell cancer of the cervix with evaluable disease, no coagulopathy, and adequate renal, hepatic, and hematological function were eligible. One course of treatment consisted of an i.v. infusion of TNP-470 over 60 min every other day for 28 days, followed by a 14-day rest period. The starting dose was 9.3 mg/m2. Eighteen evaluable patients were treated, with a median age of 48 years (range 27-55) and performance status Zubrod 1 (range 0-2). Grade 3 neurotoxicities consisting of weakness, nystagmus, diplopia, and ataxia were encountered in two patients receiving the 71.2 mg/m2 dose. An intermediate dose level of 60 mg/m2 was evaluated and found to be well tolerated by three patients. Only one patient experienced grade 3 nausea on the 60 mg/m2 dose level. No myelosuppression, retinal hemorrhage, weight loss, or significant alopecia were observed. One patient had a complete response, which continues for 26 months, and three patients with initially progressive disease stage had stable disease for 5, 7.7, and 19+ months. Other Phase I studies, including over 200 patients, were performed concurrently with this study. Based on this experience, the dose of TNP- 470 recommended for further studies is 60 mg/m2 as a 60-min i.v. infusion every Monday, Wednesday, and Friday. Neurotoxicity was dose limiting, but appears to be reversible. Otherwise, the treatment was well tolerated. The drug may be active in squamous cell cancer of the cervix. Further studies of TNP-470 in squamous cell cancer of the cervix are warranted.

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Kudelka AP, Levy T, Verschraegen CF, Edwards CL, Piamsomboon S, Termrungruanglert W et al. A phase I study of TNP-470 administered to patients with advanced squamous cell cancer of the cervix. Clinical Cancer Research. 1997 Sep 1;3(9):1501-1505.