Gender-specific acute organ toxicity during intensified preoperative radiochemotherapy for rectal cancer

Abstract

Patients with locally advanced rectal cancer (cUICC stages II/III) are typically treated with preoperative 5-fluorouracil-based (5-FU-based) radiochemotherapy (RCT). However, trials are currently being conducted to improve the complete remission rates and the systemic control by combining 5-FU with oxaliplatin. The primary objective was to identify the subgroups of rectal cancer patients who were at risk for high-grade toxicity. All 196 patients who were included in the present study were treated with 50.4 Gy and chemotherapy that included either 5-FU (n = 115) or 5-FU+oxaliplatin (n = 81). The preoperative RCT was followed by a total mesorectal excision and adjuvant chemotherapy. Acute toxicity was monitored weekly and a toxicity grade ≥3 (Common Toxicity Criteria) for a skin reaction, cystitis, proctitis, or enteritis was defined as high-grade acute organ toxicity. After RCT with 5-FU+oxaliplatin, complete tumor remission was achieved in 13.6% of the patients and in 11.3% after RCT with 5-FU alone. Complete irradiation dosages of 50.4 Gy were given to 99% (5-FU) and 95% (5-FU+oxaliplatin) of the patients. Concomitant chemotherapy was fully administered in 95% of the patients treated with 5-FU compared with the 84% of patients treated with 5-FU+oxaliplatin. A significantly higher proportion of acute organ toxicity was found in the patients who were treated with 5-FU+oxaliplatin compared with those who were treated with 5-FU. Additionally, women with a low body mass index were at the highest risk for acute organ toxicity. These results suggest that there are basic clinical parameters, such as gender and body mass index, that may be potential markers for generating individual risk profiles of RCT-induced toxicity.

Conflict of interest statement

Disclosures

Hendrik A. Wolff: None; Lena-Christin Conradi: None; Markus Schirmer: None; Tim Beissbarth: None; Thilo Sprenger: None; Margret Rave-Fränk: None; Steffen Hennies: None; Clemens F. Hess: None; Heinz Becker: None; Hans Christiansen: None; Torsten Liersch: None.

Section Editor Richard Goldberg discloses a consulting relationship with Amgen, Bayer, Genentech, Genomic Health, Lilly, and sanofi-aventis; and research funding from Amgen, Bayer, Genentech, sanofi-aventis, and Enzon.

Section Editor Patrick Johnston discloses employment with Almac Diagnostics; intellectual property including 12 patents; a consulting relationship with Almac, Roche, Chugai Pharmaceuticals, and sanofi-aventis; honoraria received from AstraZeneca, Chugai Pharmaceuticals, Pfizer, sanofi-aventis, Roche, and ASCO; research funding from AstraZeneca and Amgen; and ownership interests in Almac Diagnostics and Fusion Antibodies.

Section Editor Peter O'Dwyer discloses a consulting relationship with Tetralogic Pharmaceuticals, PrECOG, and AstraZeneca; an advisory relationship with Nereus Pharmaceutical, Tetralogic Pharmaceuticals, and PrECOG; research support from Pfizer, Bristol-Myers Squibb, Methylgene, Novartis, Genentech, Bayer, Merck, Kosan, Ardea, and Exelixis; honoraria received from Genentech, Bayer, Methylgene, and Bristol-Myers Squibb; and ownership interest with Tetralogic Pharmaceuticals.

Reviewer “A” discloses honoraria received from Roche.

Reviewer “B” discloses honoraria received from Roche and sanofi-aventis and a consulting role with Genentech.

The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias. On the basis of disclosed information, all conflicts of interest have been resolved.

Figures

Figure 1.

Treatment of studied patients. One hundred fifteen patients underwent preoperative RCT with 5-FU monotherapy and concomitant radiotherapy. Five to 6 weeks after completion of RCT, all patients underwent surgery. Adjuvant chemotherapy consisted of either 5-FU monotherapy or a combination of 5-FU with additional oxaliplatin. Abbreviations: 5-FU, 5-fluorouracil; d, day; RCT, radiochemotherapy; TME, total mesorectal excision.

Figure 2.

Acute toxicity for all patients subjected to gender and body mass indices. p-values for the two groups male and female were computed using the Kruskal-Wallis test.