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In Reply

Massachusetts General Hospital Cancer Center, Boston, MA

Donna Niedzwiecki

Duke University Medical Center, Durham, NC

Donna Hollis

Cancer and Leukemia Group B Statistical Center, Duke University Medical Center, Durham, NC

Joel Tepper

University of North Carolina, Chapel Hill, NC

Robert J. Mayer

Dana-Farber Cancer Institute, Boston, MA

We thank Drs Aschele and Lonardi for their comments on our article, "Phase I/II Study of Preoperative Oxaliplatin, Fluorouracil, and External-Beam Radiation Therapy in Patients With Locally Advanced Rectal Cancer: Cancer and Leukemia Group B 89901."¹ We agree that the pathologic complete response rate with a weekly oxaliplatin regimen demonstrated in their single institution study was similar to our multi-institutional study and provides substantial basis for the ongoing National Surgical Adjuvant Breast and Bowel Project R-04 and Studio Terapia Adiuvante Retto (STAR) trials.^1,2

These two studies did demonstrate slightly different rates of toxicity despite using the same common toxicity criteria. Drs Aschele and Lonardi suggest a number of plausible explanations for these differences and are correct in stating that we fixed the dose of fluorouracil (FU). We did not escalate the oxaliplatin dose beyond 60 mg/m² in our phase I portion despite never reaching the maximum-tolerated dose. Data from trials of FU and oxaliplatin in the metastatic setting suggested that the tolerable dose of weekly oxaliplatin with a FU regimen was between 50 mg/m² and 60 mg/m².^3,4 For this cohort of patients with curable rectal cancers, we did not want to compromise the treatment program to demonstrate the highest possible dose and therefore decided to stop the escalation at 60 mg/m². The subsequent finding in the phase II portion of our study—that 44% of patients could not complete the planned 6 weeks of oxaliplatin because of toxicity—supports this decision.

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

Although all authors completed the disclosure declaration, the following author or immediate family members indicated a financial interest. No conflict exists for drugs or devices used in a study if they are not being evaluated as part of the investigation. For a detailed description of the disclosure categories, or for more information about ASCO's conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors.

Employment: N/A Leadership: N/A Consultant: Joel Tepper, sanofi aventis Stock: N/A Honoraria: N/A Research Funds: N/A Testimony: N/A Other: David P. Ryan [speaker], sanofi aventis

REFERENCES

1. Ryan DP, Niedzwiecki D, Hollis D, et al: Phase I/II study of preoperative oxaliplatin, fluorouracil, and external-beam radiation therapy in patients with locally advanced rectal cancer: Cancer and Leukemia Group B 89901. J Clin Oncol 24:2557-2562, 2006[Abstract/Free Full Text]

2. Aschele C, Friso ML, Pucciarelli S, et al: A phase I-II study of weekly oxaliplatin, 5-fluorouracil continuous infusion and preoperative radiotherapy in locally advanced rectal cancer. Ann Oncol 16:1140-1146, 2005[Abstract/Free Full Text]

3. Chiara S, Nobile MT, Gozza A, et al: Phase II study of weekly oxaliplatin and high-dose infusional 5-fluorouracil plus leucovorin in pretreated patients with metastatic colorectal cancer. Anticancer Res 24:355-360, 2004[Abstract/Free Full Text]

4. Janinis J, Papakostas P, Samelis G, et al: Second-line chemotherapy with weekly oxaliplatin and high-dose 5-fluorouracil with folinic acid in metastatic colorectal carcinoma: A Hellenic Cooperative Oncology Group (HeCOG) phase II feasibility study. Ann Oncol 11:163-167, 2000[Abstract/Free Full Text]

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This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Ryan, D. P. Articles by Mayer, R. J. Search for Related Content PubMed Articles by Ryan, D. P. Articles by Mayer, R. J. Social Bookmarking                            What's this?