Paclitaxel, carboplatin, 5-fluorouracil, and radiation for locally advanced esophageal cancer: Phase II results of preliminary pharmacologic and molecular efforts to mitigate toxicity and predict outcomes: North Central Cancer Treatment Group (N0044)

Aminah Jatoi, James A. Martenson, Nathan R. Foster, Howard L. McLeod, Bradley S. Lair, Frank Nichols, Loren K. Tschetter, Dennis F. Moore, Tom R. Fitch, Steven Robert Alberts

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

PURPOSE: Locally advanced esophageal cancer is challenging to treat. This study tested a 3-drug, multimodality approach. Chemotherapy dose reductions, the addition of amifostine, and pharmacogenetics were tested in an effort to mitigate toxicity and predict outcomes. PATIENTS AND METHODS: This phase II trial tested chemotherapy (carboplatin area under the curve = 4 [lower dose than that from Meluch et al] on day 1 and 22, 5-fluorouracil 225 mg/m per day continuous infusion on days 1 to 42, and paclitaxel 200 mg/m on days 1 and 22) with concomitant radiation 4500 cG for locally advanced esophageal cancer. Esophagectomy was scheduled after radiation. Amifostine 500 mg subcutaneously before radiation was given to the first 19 patients. RESULTS: Among 54 eligible patients, the pathologic complete response rate was 35% (95% confidence interval [CI], 23%-49%). Median survival was 21.2 months (95% CI, 13.6-37.6 months), and median time to cancer recurrence/progression 19 months (95% CI, 11.4-44.6 months). Nearly all patients (94%) suffered at least one grade 3 or worse adverse event, including 3 treatment-related deaths. Amifostine was discontinued because of one of these deaths. There was no statistically significant difference in the rates of severe adverse events among patients who received amifostine and those who did not. Genotyping for polymorphisms of dihydropyrimidine dehydrogenase, cytochrome P3A4, and glutathione-S-transferase did not predict tumor response or severe adverse events. CONCLUSIONS: This 3-drug, multimodality approach yielded a pathologic complete response rate of 35%, but the severe adverse event rate was high. Utilizing amifostine to reduce toxicity or employing molecular approaches to predict outcomes did not show promise.

Original languageEnglish (US)
Pages (from-to)507-513
Number of pages7
JournalAmerican Journal of Clinical Oncology: Cancer Clinical Trials
Volume30
Issue number5
DOIs
StatePublished - Oct 2007

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Amifostine
Carboplatin
Esophageal Neoplasms
Paclitaxel
Fluorouracil
Radiation
Confidence Intervals
Neoplasms
Dihydrouracil Dehydrogenase (NADP)
Therapeutics
Drug Therapy
Esophagectomy
Pharmacogenetics
Cytochromes
Glutathione Transferase
Pharmaceutical Preparations
Area Under Curve
Recurrence
Survival

Keywords

  • Amifostine
  • Chemotherapy
  • Esophageal cancer
  • Locally advanced

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Paclitaxel, carboplatin, 5-fluorouracil, and radiation for locally advanced esophageal cancer : Phase II results of preliminary pharmacologic and molecular efforts to mitigate toxicity and predict outcomes: North Central Cancer Treatment Group (N0044). / Jatoi, Aminah; Martenson, James A.; Foster, Nathan R.; McLeod, Howard L.; Lair, Bradley S.; Nichols, Frank; Tschetter, Loren K.; Moore, Dennis F.; Fitch, Tom R.; Alberts, Steven Robert.

In: American Journal of Clinical Oncology: Cancer Clinical Trials, Vol. 30, No. 5, 10.2007, p. 507-513.

Research output: Contribution to journalArticle

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abstract = "PURPOSE: Locally advanced esophageal cancer is challenging to treat. This study tested a 3-drug, multimodality approach. Chemotherapy dose reductions, the addition of amifostine, and pharmacogenetics were tested in an effort to mitigate toxicity and predict outcomes. PATIENTS AND METHODS: This phase II trial tested chemotherapy (carboplatin area under the curve = 4 [lower dose than that from Meluch et al] on day 1 and 22, 5-fluorouracil 225 mg/m per day continuous infusion on days 1 to 42, and paclitaxel 200 mg/m on days 1 and 22) with concomitant radiation 4500 cG for locally advanced esophageal cancer. Esophagectomy was scheduled after radiation. Amifostine 500 mg subcutaneously before radiation was given to the first 19 patients. RESULTS: Among 54 eligible patients, the pathologic complete response rate was 35{\%} (95{\%} confidence interval [CI], 23{\%}-49{\%}). Median survival was 21.2 months (95{\%} CI, 13.6-37.6 months), and median time to cancer recurrence/progression 19 months (95{\%} CI, 11.4-44.6 months). Nearly all patients (94{\%}) suffered at least one grade 3 or worse adverse event, including 3 treatment-related deaths. Amifostine was discontinued because of one of these deaths. There was no statistically significant difference in the rates of severe adverse events among patients who received amifostine and those who did not. Genotyping for polymorphisms of dihydropyrimidine dehydrogenase, cytochrome P3A4, and glutathione-S-transferase did not predict tumor response or severe adverse events. CONCLUSIONS: This 3-drug, multimodality approach yielded a pathologic complete response rate of 35{\%}, but the severe adverse event rate was high. Utilizing amifostine to reduce toxicity or employing molecular approaches to predict outcomes did not show promise.",
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T2 - Phase II results of preliminary pharmacologic and molecular efforts to mitigate toxicity and predict outcomes: North Central Cancer Treatment Group (N0044)

AU - Jatoi, Aminah

AU - Martenson, James A.

AU - Foster, Nathan R.

AU - McLeod, Howard L.

AU - Lair, Bradley S.

AU - Nichols, Frank

AU - Tschetter, Loren K.

AU - Moore, Dennis F.

AU - Fitch, Tom R.

AU - Alberts, Steven Robert

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N2 - PURPOSE: Locally advanced esophageal cancer is challenging to treat. This study tested a 3-drug, multimodality approach. Chemotherapy dose reductions, the addition of amifostine, and pharmacogenetics were tested in an effort to mitigate toxicity and predict outcomes. PATIENTS AND METHODS: This phase II trial tested chemotherapy (carboplatin area under the curve = 4 [lower dose than that from Meluch et al] on day 1 and 22, 5-fluorouracil 225 mg/m per day continuous infusion on days 1 to 42, and paclitaxel 200 mg/m on days 1 and 22) with concomitant radiation 4500 cG for locally advanced esophageal cancer. Esophagectomy was scheduled after radiation. Amifostine 500 mg subcutaneously before radiation was given to the first 19 patients. RESULTS: Among 54 eligible patients, the pathologic complete response rate was 35% (95% confidence interval [CI], 23%-49%). Median survival was 21.2 months (95% CI, 13.6-37.6 months), and median time to cancer recurrence/progression 19 months (95% CI, 11.4-44.6 months). Nearly all patients (94%) suffered at least one grade 3 or worse adverse event, including 3 treatment-related deaths. Amifostine was discontinued because of one of these deaths. There was no statistically significant difference in the rates of severe adverse events among patients who received amifostine and those who did not. Genotyping for polymorphisms of dihydropyrimidine dehydrogenase, cytochrome P3A4, and glutathione-S-transferase did not predict tumor response or severe adverse events. CONCLUSIONS: This 3-drug, multimodality approach yielded a pathologic complete response rate of 35%, but the severe adverse event rate was high. Utilizing amifostine to reduce toxicity or employing molecular approaches to predict outcomes did not show promise.

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