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Oxaliplatin and capecitabine concomitant with neoadjuvant radiotherapy and extended to the resting period in high risk locally advanced rectal cancer

Oxaliplatin und Capecitabin begleitend zur neoadjuvanten Radiotherapie und deren Ausweitung auf die Ruhephase beim lokal fortgeschrittenen High-Risk-Rektumkarzinom

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Abstract

Background

Conventional neoadjuvant chemoradiotherapy (CRT) is suboptimal for systemic control in locally advanced rectal cancer (LARC). To improve systemic control, we developed an alternative approach in which an intensified oxaliplatin and capecitabine (XELOX) chemotherapy regimen was administered concomitantly with radiation and extended to the resting period (consolidation chemotherapy) for high-risk LARC. The aim of the current study was to evaluate the short-term efficacy and toxicity of this strategy.

Methods

Patients with high-risk LARC were treated with CRT. Two cycles of XELOX were administered concomitantly with radiation. Thereafter, an additional cycle of the same regimen was administered during the resting period after completion of CRT. Tumor response, toxicities and surgical complications were recorded.

Results

This study includes 36 patients treated with the above strategy. All patients completed the planned concurrent CRT. Because of grade 3 toxicities, 2 patients were unable to complete the additional chemotherapy. Grade 3 toxicities were leucopenia (2.8 %), diarrhea (2.8 %) and radiodermatitis (2.8 %). All patients underwent optimal surgery with total mesorectal excision (TME) and a sphincter-saving procedure was performed in 27 patients (75 %). There was no perioperative mortality. Postoperative complications developed in 7 patients (19.4 %). Pathologic complete regression (pCR),“nearly pCR” (major regression), and moderate or minimal regression were achieved in 13 (36.1 %), 16 (44.4 %), and 7 patients (19.5 %), respectively.

Conclusion

The preliminary results suggest that a XELOX regimen initially administered concomitantly with radiotherapy and then extended to the resting period in high-risk LARC patients is well tolerated. The strategy is highly effective in terms of pCR and nearly pCR rates, and thus warrants further investigation.

Zusammenfassung

Hintergrund

Konventionell neoadjuvante Radiochemotherapie (CRT) ist suboptimal für die systemische Kontrolle des lokal fortgeschrittenen Rektumkarzinoms (LARC). Um die systemische Kontrolle zu verbessern, haben wir eine alternative Herangehensweise entwickelt, in welcher wir eine intensivierte Chemotherapie mit dem XELOX-Therapieschema (Oxaliplatin und Capecitabin) begleitend zur Bestrahlung kombiniert und auf die Ruhephase des High-Risk-LARC ausgeweitet haben (Konsolidierungschemotherapie). Das Ziel der Studie stellte die Evaluierung der Kurzzeit-Wirksamkeit und der Toxizität dieser Vorgehensweise dar.

Patienten und Methoden

Patienten mit High-Risk-LARC wurden mit einer CRT behandelt. Begleitend zur Bestrahlung wurden 2 Therapiezyklen XELOX verabreicht. Anschließend wurde ein zusätzlicher Therapiezyklus über die Ruhephase nach Abschluss der CRT verabreicht. Erfasst wurden Tumorantwort, Toxizität und Komplikationen beim Eingriff.

Ergebnisse

Es wurden 36 Patienten ermittelt, welche mit dieser Methode behandelt wurden. Alle Patienten komplettierten die begleitende CRT. Aufgrund von Grad-3-Toxizitäten konnten 2 Patienten die zusätzliche Chemotherapie nicht abschließen. Toxizitäten dritten Grades waren Leukozytopenie (2,8 %), Diarrhoe (2,8 %) und Radiodermatitis (2,8 %). Allen Patienten wurde eine optimale chirurgische Therapie durch totale mesorektale Exzision („total mesorectal excision“, TME) zuteil, unter ihnen befanden sich 27 Patienten (75 %), die spinktererhaltend operiert werden konnten. Es gab keine perioperative Mortalität in der Kohorte. Bei 7 Patienten (19,4 %) traten postoperative Komplikationen auf. Eine pathologisch vollständige Regression (pCR), überwiegende Regression (“nearly pCR“) und mäßige oder minimale Regression wurde bei je 13 (36,1 %), 16 (44,4 %) und 7 (19,5 %) Patienten erreicht.

Schlussfolgerung

Die vorläufigen Ergebnisse legen den Schluss nahe, dass ein Therapieschema mit XELOX begleitend zur Radiotherapie, ausgeweitet auf die Ruhephase bei High-Risk-LARC gut toleriert wird. Die Methode ist höchst effektiv in Bezug auf pCR- und überwiegende pCR-Raten. Somit sind weitere Untersuchungen gerechtfertigt.

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Acknowledgments

The authors would like to acknowledge Andrea Schott and Senchao Lai for the German translation.

Financial disclosures

Grant support: This work was supported by funds from the Nature Science Foundation of China (No. 81101591); the Natural Science Foundation of Guangdong Province, China (No.S2011040005278; No. 9151008901000157) and the Science and Technology Planning Project of Guangdong Province, China (No.2010B060900043).

Compliance with ethical guidelines

Conflict of interests. Yuan-Hong Gao, Xu Zhang, Xin An, Mu-Yan Cai, Zhi-Fan Zeng, Gong Chen, Ling-Heng Kong, Jun-Zhong Lin, De-Sen Wan, Zhi-Zhong Pan and Pei-Rong Ding state that there are no conflicts of interest.

All studies on humans described in the present manuscript were carried out with the approval of the responsible ethics committee and in accordance with national law and the Helsinki Declaration of 1975 (in its current, revised form). Informed consent was obtained from all patients included in studies.

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Authors and Affiliations

  1. State Key Laboratory of Oncology in South China, 651 Dongfeng Road East, 510060, Guangzhou, P.R. China

    Y.-H. Gao, X. Zhang, X. An, M.-Y. Cai, Z.-F. Zeng, G. Chen, L.-H. Kong, J.-Z. Lin, D.-S. Wan, Z.-Z. Pan MD &  P.-R. Ding MD

  2. Departments of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China

    Y.-H. Gao & Z.-F. Zeng

  3. Departments of Thoracic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China

    X. Zhang

  4. Departments of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China

    X. An

  5. Departments of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China

    M.-Y. Cai

  6. Departments of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China

    G. Chen, L.-H. Kong, J.-Z. Lin, D.-S. Wan, Z.-Z. Pan MD &  P.-R. Ding MD

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  1. Y.-H. Gao
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Corresponding author

Correspondence to Z.-Z. Pan MD.

Additional information

Yuan-Hong Gao, Xu Zhang and Xin An contributed equally to this work.

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Gao, YH., Zhang, X., An, X. et al. Oxaliplatin and capecitabine concomitant with neoadjuvant radiotherapy and extended to the resting period in high risk locally advanced rectal cancer. Strahlenther Onkol 190, 158–164 (2014). https://doi.org/10.1007/s00066-013-0500-5

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  • DOI: https://doi.org/10.1007/s00066-013-0500-5

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