Activity of Sorafenib Plus Capecitabine in Previously Treated Metastatic Colorectal Cancer

Thomas J George; Alison M Ivey; Azka Ali; Ji-Hyun Lee; Yu Wang; Karen C Daily; Brian H Ramnaraign; Sanda A Tan; Krista P Terracina; Thomas E Read; Long H Dang; Atif Iqbal

doi:10.1002/onco.13689

Activity of Sorafenib Plus Capecitabine in Previously Treated Metastatic Colorectal Cancer

Oncologist. 2021 May;26(5):362-e724. doi: 10.1002/onco.13689. Epub 2021 Feb 22.

Authors

Thomas J George^{1

2}, Alison M Ivey², Azka Ali^{1

2}, Ji-Hyun Lee^{3

4}, Yu Wang⁴, Karen C Daily^{1

2}, Brian H Ramnaraign^{1

2}, Sanda A Tan⁵, Krista P Terracina⁵, Thomas E Read⁵, Long H Dang⁶, Atif Iqbal^{7

8}

Affiliations

¹ Division of Hematology Oncology, Department of Medicine, University of Florida Cancer Center, Gainesville, Florida, USA.
² University of Florida Health Cancer Center, Gainesville, Florida, USA.
³ Department of Biostatistics, University of Florida, Gainesville, Florida, USA.
⁴ Division of Quantitative Sciences, UF Health Cancer Center, Gainesville, Florida, USA.
⁵ Department of Surgery, University of Florida, Gainesville, Florida, USA.
⁶ Department of Surgery, University of Florida, Gainesville, Florida, USA.
⁷ Department of Oncology, Ochsner Health, Baton Rouge, Louisiana, Texas, USA.
⁸ Department of Surgery, Baylor University, Houston, Texas, USA.

Abstract

Lessons learned: Treatment for patients with metastatic colorectal cancer (mCRC) typically involves multiple lines of therapy with eventual development of treatment resistance. In this single-arm, phase II study involving heavily pretreated patients, the combination of sorafenib and capecitabine yielded a clinically meaningful progression-free survival of 6.2 months with an acceptable toxicity profile. This oral doublet therapy is worthy of continued investigation for clinical use in patients with mCRC.

Background: Capecitabine (Cape) is an oral prodrug of the antimetabolite 5-fluorouracil. Sorafenib (Sor) inhibits multiple signaling pathways involved in angiogenesis and tumor proliferation. SorCape has been previously studied in metastatic breast cancer.

Methods: This single-arm, phase II study was designed to evaluate the activity of SorCape in refractory metastatic colorectal cancer (mCRC). Patients received Sor (200 mg p.o. b.i.d. max daily) and Cape (1,000 mg/m² p.o. b.i.d. on days 1-14) on a 21-day treatment cycle. Primary endpoint was progression-free survival (PFS) with preplanned comparison with historical controls.

Results: Forty-two patients were treated for a median number of 3.5 cycles (range 1-39). Median PFS was 6.2 (95% confidence interval [CI], 4.3-7.9) months, and overall survival (OS) was 8.8 (95% CI, 4.3-12.2) months. One patient (2.4%) had partial response (PR), and 22 patients (52.4%) had stable disease (SD) for a clinical benefit rate of 54.8% (95% CI, 38.7%-70.2%). Hand-foot syndrome was the most common adverse event seen in 36 patients (85.7%) and was grade ≥ 3 in 16 patients (38.1%). One patient (2.4%) had a grade 4 sepsis, and one patient (2.4%) died while on treatment.

Conclusion: SorCape in this heavily pretreated population yielded a reasonable PFS with manageable but notable toxicity. The combination should be investigated further.

Keywords: Capecitabine; Colorectal cancer; Metastatic cancer; Oral therapy; Sorafenib.

Publication types

Clinical Trial, Phase II

MeSH terms

Antineoplastic Combined Chemotherapy Protocols / adverse effects
Capecitabine / therapeutic use
Colorectal Neoplasms* / drug therapy
Deoxycytidine* / therapeutic use
Fluorouracil / therapeutic use
Humans
Sorafenib / therapeutic use
Treatment Outcome

Substances

Deoxycytidine
Capecitabine
Sorafenib
Fluorouracil