Trastuzumab, paclitaxel, carboplatin, and gemcitabine in advanced human epidermal growth factor receptor-2/neu-positive urothelial carcinoma

Results of a multicenter phase II National Cancer Institute trial

Maha H A Hussain, Gary R. MacVicar, Daniel P. Petrylak, Rodney L. Dunn, Ulka Vaishampayan, Primo N Lara, Gurkamal S. Chatta, David M. Nanus, L. Michael Glode, Donald L. Trump, Helen Chen, David C. Smith

Research output: Contribution to journalArticle

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Abstract

Purpose: We investigated the safety and efficacy (response rates, time to disease progression, survival) of trastuzumab, carboplatin, gemcitabine, and paclitaxel in advanced urothelial carcinoma patients and prospectively evaluated human epidermal growth factor receptor-2 (Her-2/neu) overexpression rates. Patients and Methods: Advanced urothelial carcinoma patients were screened for Her-2/neu overexpression. Eligibility for therapy required human epidermal growth factor receptor-2 (Her-2/neu) overexpression by immunohistochemistry (IHC), gene amplification and/or elevated serum Her-2/neu, no prior chemotherapy for metastasis, and adequate organ function including a normal cardiac function. Treatment consisted of trastuzumab (T) 4 mg/kg loading dose followed by 2 mg/kg on days 1, 8, and 15; paclitaxel (P) 200 mg/m2 on day 1; carboplatin (C; area under the curve, 5) on day 1; and gemcitabine (G) 800 mg/m2 on days 1 and 8. The primary end point was cardiac toxicity. Results: Fifty-seven (52.3%) of 109 registered patients were Her-2/neu positive, and 48.6% were positive by IHC. Her-2/neu-positive patients had more metastatic sites and visceral metastasis than did Her-2/neu negative patients. Forty-four of 57 Her-2/neu-positive patients were treated with TPCG. The median number of cycles was six (range, 1 to 12 cycles). The most common grade 3/4 toxicity was myelosuppression. Grade 3 sensory neuropathy occurred in 14% of patients, and 22.7% experienced grade 1 to 3 cardiac toxicity (grade 3, n = 2: one left ventricular dysfunction, one tachycardia). There were two therapy-related deaths. Thirty-one (70%) of 44 patients responded (five complete and 26 partial), and 25 (57%) of 44 were confirmed responses. Median time to progression and survival were 9.3 and 14.1 months, respectively. Conclusion: We prospectively characterized Her-2/neu status in advanced urothelial carcinoma patients. TPCG is feasible; cardiac toxicity rates were higher than projected, but the majority were grade two or lower. Determining the true contribution of trastuzumab requires a randomized trial.

Original languageEnglish (US)
Pages (from-to)2218-2224
Number of pages7
JournalJournal of Clinical Oncology
Volume25
Issue number16
DOIs
StatePublished - Jun 1 2007
Externally publishedYes

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gemcitabine
National Cancer Institute (U.S.)
Carboplatin
Paclitaxel
Carcinoma
Immunohistochemistry
human ERBB2 protein
Trastuzumab
Neoplasm Metastasis
Survival
Gene Amplification
Left Ventricular Dysfunction

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Trastuzumab, paclitaxel, carboplatin, and gemcitabine in advanced human epidermal growth factor receptor-2/neu-positive urothelial carcinoma : Results of a multicenter phase II National Cancer Institute trial. / Hussain, Maha H A; MacVicar, Gary R.; Petrylak, Daniel P.; Dunn, Rodney L.; Vaishampayan, Ulka; Lara, Primo N; Chatta, Gurkamal S.; Nanus, David M.; Glode, L. Michael; Trump, Donald L.; Chen, Helen; Smith, David C.

In: Journal of Clinical Oncology, Vol. 25, No. 16, 01.06.2007, p. 2218-2224.

Research output: Contribution to journalArticle

Hussain, Maha H A ; MacVicar, Gary R. ; Petrylak, Daniel P. ; Dunn, Rodney L. ; Vaishampayan, Ulka ; Lara, Primo N ; Chatta, Gurkamal S. ; Nanus, David M. ; Glode, L. Michael ; Trump, Donald L. ; Chen, Helen ; Smith, David C. / Trastuzumab, paclitaxel, carboplatin, and gemcitabine in advanced human epidermal growth factor receptor-2/neu-positive urothelial carcinoma : Results of a multicenter phase II National Cancer Institute trial. In: Journal of Clinical Oncology. 2007 ; Vol. 25, No. 16. pp. 2218-2224.
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abstract = "Purpose: We investigated the safety and efficacy (response rates, time to disease progression, survival) of trastuzumab, carboplatin, gemcitabine, and paclitaxel in advanced urothelial carcinoma patients and prospectively evaluated human epidermal growth factor receptor-2 (Her-2/neu) overexpression rates. Patients and Methods: Advanced urothelial carcinoma patients were screened for Her-2/neu overexpression. Eligibility for therapy required human epidermal growth factor receptor-2 (Her-2/neu) overexpression by immunohistochemistry (IHC), gene amplification and/or elevated serum Her-2/neu, no prior chemotherapy for metastasis, and adequate organ function including a normal cardiac function. Treatment consisted of trastuzumab (T) 4 mg/kg loading dose followed by 2 mg/kg on days 1, 8, and 15; paclitaxel (P) 200 mg/m2 on day 1; carboplatin (C; area under the curve, 5) on day 1; and gemcitabine (G) 800 mg/m2 on days 1 and 8. The primary end point was cardiac toxicity. Results: Fifty-seven (52.3{\%}) of 109 registered patients were Her-2/neu positive, and 48.6{\%} were positive by IHC. Her-2/neu-positive patients had more metastatic sites and visceral metastasis than did Her-2/neu negative patients. Forty-four of 57 Her-2/neu-positive patients were treated with TPCG. The median number of cycles was six (range, 1 to 12 cycles). The most common grade 3/4 toxicity was myelosuppression. Grade 3 sensory neuropathy occurred in 14{\%} of patients, and 22.7{\%} experienced grade 1 to 3 cardiac toxicity (grade 3, n = 2: one left ventricular dysfunction, one tachycardia). There were two therapy-related deaths. Thirty-one (70{\%}) of 44 patients responded (five complete and 26 partial), and 25 (57{\%}) of 44 were confirmed responses. Median time to progression and survival were 9.3 and 14.1 months, respectively. Conclusion: We prospectively characterized Her-2/neu status in advanced urothelial carcinoma patients. TPCG is feasible; cardiac toxicity rates were higher than projected, but the majority were grade two or lower. Determining the true contribution of trastuzumab requires a randomized trial.",
author = "Hussain, {Maha H A} and MacVicar, {Gary R.} and Petrylak, {Daniel P.} and Dunn, {Rodney L.} and Ulka Vaishampayan and Lara, {Primo N} and Chatta, {Gurkamal S.} and Nanus, {David M.} and Glode, {L. Michael} and Trump, {Donald L.} and Helen Chen and Smith, {David C.}",
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T1 - Trastuzumab, paclitaxel, carboplatin, and gemcitabine in advanced human epidermal growth factor receptor-2/neu-positive urothelial carcinoma

T2 - Results of a multicenter phase II National Cancer Institute trial

AU - Hussain, Maha H A

AU - MacVicar, Gary R.

AU - Petrylak, Daniel P.

AU - Dunn, Rodney L.

AU - Vaishampayan, Ulka

AU - Lara, Primo N

AU - Chatta, Gurkamal S.

AU - Nanus, David M.

AU - Glode, L. Michael

AU - Trump, Donald L.

AU - Chen, Helen

AU - Smith, David C.

PY - 2007/6/1

Y1 - 2007/6/1

N2 - Purpose: We investigated the safety and efficacy (response rates, time to disease progression, survival) of trastuzumab, carboplatin, gemcitabine, and paclitaxel in advanced urothelial carcinoma patients and prospectively evaluated human epidermal growth factor receptor-2 (Her-2/neu) overexpression rates. Patients and Methods: Advanced urothelial carcinoma patients were screened for Her-2/neu overexpression. Eligibility for therapy required human epidermal growth factor receptor-2 (Her-2/neu) overexpression by immunohistochemistry (IHC), gene amplification and/or elevated serum Her-2/neu, no prior chemotherapy for metastasis, and adequate organ function including a normal cardiac function. Treatment consisted of trastuzumab (T) 4 mg/kg loading dose followed by 2 mg/kg on days 1, 8, and 15; paclitaxel (P) 200 mg/m2 on day 1; carboplatin (C; area under the curve, 5) on day 1; and gemcitabine (G) 800 mg/m2 on days 1 and 8. The primary end point was cardiac toxicity. Results: Fifty-seven (52.3%) of 109 registered patients were Her-2/neu positive, and 48.6% were positive by IHC. Her-2/neu-positive patients had more metastatic sites and visceral metastasis than did Her-2/neu negative patients. Forty-four of 57 Her-2/neu-positive patients were treated with TPCG. The median number of cycles was six (range, 1 to 12 cycles). The most common grade 3/4 toxicity was myelosuppression. Grade 3 sensory neuropathy occurred in 14% of patients, and 22.7% experienced grade 1 to 3 cardiac toxicity (grade 3, n = 2: one left ventricular dysfunction, one tachycardia). There were two therapy-related deaths. Thirty-one (70%) of 44 patients responded (five complete and 26 partial), and 25 (57%) of 44 were confirmed responses. Median time to progression and survival were 9.3 and 14.1 months, respectively. Conclusion: We prospectively characterized Her-2/neu status in advanced urothelial carcinoma patients. TPCG is feasible; cardiac toxicity rates were higher than projected, but the majority were grade two or lower. Determining the true contribution of trastuzumab requires a randomized trial.

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