Neoadjuvant capecitabine combined with standard radiotherapy in patients with locally advanced rectal cancer: mature results of a phase II trial.

Abstract

PURPOSE:

The objective of this expanded phase II trial was to confirm the safety results of the preceding phase I study and establish the efficacy of neoadjuvant radiochemotherapy with capecitabine in rectal cancer in a multicenter setting.

PATIENTS AND METHODS:

96 patients (63% male, age 34-81 years) with advanced rectal cancer (cT3-4 or cN+) from seven university centers in Germany were recruited. All were to receive a total irradiation dose of 50.4-55.8 Gy with conventional fractions. Capecitabine was given at an oral dosage of 825 mg/m(2)bid on each day of the radiotherapy period with the first daily dose applied 2 h before irradiation, followed by surgery 6 weeks later.

RESULTS:

Most of the patients suffered from an advanced primary tumor (cT3: 57%, cT4: 40%) with lymph node involvement in 60%. After neoadjuvant treatment, with a mean of 99% of the scheduled radiation dose actually delivered, a clinical response rate of 68% (95% confidence interval: 57-78%) was observed. Out of 87 evaluable patients undergoing surgery, a sphincter-preserving procedure could be performed in 51% and R0 resection in 94%. A pathologically complete response was achieved in six patients (7%, 95% confidence interval: 3-14%). The comparison of initial diagnosis and pathologic findings showed a downstaging in 61%. Acute toxicity with > 5% incidence of NCI (National Cancer Institute) grade >/= 3 included lymphopenia (12%), leukopenia (6%), and diarrhea (7%). Mild to moderate hand-foot syndrome occurred in 12% only. After a median follow-up of 48 months, the 5-year overall survival and tumor control data were, with regard to patient selection, in the expected range with an overall survival of 65%, a relapse-free survival of 47%, and a local recurrence rate after 5 years of 17%.

CONCLUSION:

The data clearly confirm that capecitabine is an adequate substitute for 5-fluorouracil in preoperative chemoradiation of rectal cancer with a favorable safety profile.

• Authors: Juergen Dunst, Juergen Debus, Volker Rudat, Joern Wulf, Wilfried Budach, Tobias Hoelscher, Thomas Reese, Stephan Mose, Claus Roedel, Helmut Zuehlke, Axel Hinke
• Journal: Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] (Strahlenther Onkol) Vol. 184 Issue 9 Pg. 450-6 (Sep 2008) ISSN: 1439-099X [Electronic] Germany
• PMID: 19016023 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Antimetabolites, Antineoplastic
• Deoxycytidine
• Capecitabine
• Leucovorin
• Fluorouracil

Topics

• Adenocarcinoma (drug therapy, pathology, radiotherapy, surgery)
• Adult
• Aged
• Aged, 80 and over
• Antimetabolites, Antineoplastic (adverse effects, therapeutic use)
• Capecitabine
• Chemotherapy, Adjuvant
• Deoxycytidine (adverse effects, analogs & derivatives, therapeutic use)
• Disease-Free Survival
• Dose Fractionation, Radiation
• Female
• Fluorouracil (adverse effects, analogs & derivatives, therapeutic use)
• Follow-Up Studies
• Humans
• Leucovorin (adverse effects, therapeutic use)
• Lymphatic Metastasis
• Male
• Middle Aged
• Neoadjuvant Therapy
• Neoplasm Staging
• Proctocolectomy, Restorative
• Radiotherapy Planning, Computer-Assisted
• Rectal Neoplasms (drug therapy, pathology, radiotherapy, surgery)
• Rectum (pathology, surgery)