A randomized phase II trial in patients with carcinoma of an unknown primary site

Jonathan E. Dowell, Audrey M. Garrett, Yu Shyr, David H. Johnson, Kenneth R. Hande

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

BACKGROUND. Current therapy for patients with carcinoma of an unknown primary site (CUP) is inadequate. To develop less toxic and more effective therapies for patients with CUP, a multicenter, randomized, Phase II study was conducted. Patients with CUP received either carboplatin and etoposide (CE) or a combination of paclitaxel, 5-fluorouracil, and leucovorin (TFL). METHODS. Patients randomized to Arm A received paclitaxel, 175 mg/m2, intravenously over 3 hours on Day 1 followed by leucovorin, 300 mg, over 30-60 minutes and 5-fluorouracil, 350 mg/m2, both intravenously on Days 1-3. Patients randomized to Arm B received etoposide, 100 mg/m2, intravenously on Days 1-3 and carboplatin at an area under the curve of 6 on Day 1 only. The cycles in both treatment arms were repeated every 28 days. Patients were followed for tumor response, survival, and toxicity. RESULTS. Thirty-four patients were enrolled, 32 of whom were evaluable for response. An identical overall response rate of 19% (95% confidence interval, 4-45%) was noted in each treatment arm. The median survival for the entire study population was 194 days. The median survivals observed in Arm A and Arm B were 251 days and 194 days, respectively (P = 0.91 [difference not significant]). Hematologic toxicity on Arm B was considerable with 29% of the patients developing neutropenia and fever. Toxicity on Arm A was modest. CONCLUSIONS. In this randomized Phase II trial, CE and TFL appeared to have modest activity in CUP patients, with response rates similar to those reported with previously described chemotherapy regimens. Toxicity with CE was more severe than expected, although TFL was found to be well tolerated.

Original languageEnglish (US)
Pages (from-to)592-597
Number of pages6
JournalCancer
Volume91
Issue number3
DOIs
StatePublished - Feb 1 2001

Fingerprint

Carcinoma
Carboplatin
Etoposide
Leucovorin
Paclitaxel
Fluorouracil
Survival
Poisons
Therapeutics
Neutropenia
Area Under Curve
Fever
Confidence Intervals
Drug Therapy
Population
Neoplasms

Keywords

  • 5-fluorouracil
  • Carboplatin
  • Etoposide
  • Neoplasm
  • Paclitaxel
  • Unknown primary

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

A randomized phase II trial in patients with carcinoma of an unknown primary site. / Dowell, Jonathan E.; Garrett, Audrey M.; Shyr, Yu; Johnson, David H.; Hande, Kenneth R.

In: Cancer, Vol. 91, No. 3, 01.02.2001, p. 592-597.

Research output: Contribution to journalArticle

Dowell, Jonathan E. ; Garrett, Audrey M. ; Shyr, Yu ; Johnson, David H. ; Hande, Kenneth R. / A randomized phase II trial in patients with carcinoma of an unknown primary site. In: Cancer. 2001 ; Vol. 91, No. 3. pp. 592-597.
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abstract = "BACKGROUND. Current therapy for patients with carcinoma of an unknown primary site (CUP) is inadequate. To develop less toxic and more effective therapies for patients with CUP, a multicenter, randomized, Phase II study was conducted. Patients with CUP received either carboplatin and etoposide (CE) or a combination of paclitaxel, 5-fluorouracil, and leucovorin (TFL). METHODS. Patients randomized to Arm A received paclitaxel, 175 mg/m2, intravenously over 3 hours on Day 1 followed by leucovorin, 300 mg, over 30-60 minutes and 5-fluorouracil, 350 mg/m2, both intravenously on Days 1-3. Patients randomized to Arm B received etoposide, 100 mg/m2, intravenously on Days 1-3 and carboplatin at an area under the curve of 6 on Day 1 only. The cycles in both treatment arms were repeated every 28 days. Patients were followed for tumor response, survival, and toxicity. RESULTS. Thirty-four patients were enrolled, 32 of whom were evaluable for response. An identical overall response rate of 19{\%} (95{\%} confidence interval, 4-45{\%}) was noted in each treatment arm. The median survival for the entire study population was 194 days. The median survivals observed in Arm A and Arm B were 251 days and 194 days, respectively (P = 0.91 [difference not significant]). Hematologic toxicity on Arm B was considerable with 29{\%} of the patients developing neutropenia and fever. Toxicity on Arm A was modest. CONCLUSIONS. In this randomized Phase II trial, CE and TFL appeared to have modest activity in CUP patients, with response rates similar to those reported with previously described chemotherapy regimens. Toxicity with CE was more severe than expected, although TFL was found to be well tolerated.",
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N2 - BACKGROUND. Current therapy for patients with carcinoma of an unknown primary site (CUP) is inadequate. To develop less toxic and more effective therapies for patients with CUP, a multicenter, randomized, Phase II study was conducted. Patients with CUP received either carboplatin and etoposide (CE) or a combination of paclitaxel, 5-fluorouracil, and leucovorin (TFL). METHODS. Patients randomized to Arm A received paclitaxel, 175 mg/m2, intravenously over 3 hours on Day 1 followed by leucovorin, 300 mg, over 30-60 minutes and 5-fluorouracil, 350 mg/m2, both intravenously on Days 1-3. Patients randomized to Arm B received etoposide, 100 mg/m2, intravenously on Days 1-3 and carboplatin at an area under the curve of 6 on Day 1 only. The cycles in both treatment arms were repeated every 28 days. Patients were followed for tumor response, survival, and toxicity. RESULTS. Thirty-four patients were enrolled, 32 of whom were evaluable for response. An identical overall response rate of 19% (95% confidence interval, 4-45%) was noted in each treatment arm. The median survival for the entire study population was 194 days. The median survivals observed in Arm A and Arm B were 251 days and 194 days, respectively (P = 0.91 [difference not significant]). Hematologic toxicity on Arm B was considerable with 29% of the patients developing neutropenia and fever. Toxicity on Arm A was modest. CONCLUSIONS. In this randomized Phase II trial, CE and TFL appeared to have modest activity in CUP patients, with response rates similar to those reported with previously described chemotherapy regimens. Toxicity with CE was more severe than expected, although TFL was found to be well tolerated.

AB - BACKGROUND. Current therapy for patients with carcinoma of an unknown primary site (CUP) is inadequate. To develop less toxic and more effective therapies for patients with CUP, a multicenter, randomized, Phase II study was conducted. Patients with CUP received either carboplatin and etoposide (CE) or a combination of paclitaxel, 5-fluorouracil, and leucovorin (TFL). METHODS. Patients randomized to Arm A received paclitaxel, 175 mg/m2, intravenously over 3 hours on Day 1 followed by leucovorin, 300 mg, over 30-60 minutes and 5-fluorouracil, 350 mg/m2, both intravenously on Days 1-3. Patients randomized to Arm B received etoposide, 100 mg/m2, intravenously on Days 1-3 and carboplatin at an area under the curve of 6 on Day 1 only. The cycles in both treatment arms were repeated every 28 days. Patients were followed for tumor response, survival, and toxicity. RESULTS. Thirty-four patients were enrolled, 32 of whom were evaluable for response. An identical overall response rate of 19% (95% confidence interval, 4-45%) was noted in each treatment arm. The median survival for the entire study population was 194 days. The median survivals observed in Arm A and Arm B were 251 days and 194 days, respectively (P = 0.91 [difference not significant]). Hematologic toxicity on Arm B was considerable with 29% of the patients developing neutropenia and fever. Toxicity on Arm A was modest. CONCLUSIONS. In this randomized Phase II trial, CE and TFL appeared to have modest activity in CUP patients, with response rates similar to those reported with previously described chemotherapy regimens. Toxicity with CE was more severe than expected, although TFL was found to be well tolerated.

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KW - Neoplasm

KW - Paclitaxel

KW - Unknown primary

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