Phase II Trial Using a Combination of Oxaliplatin, Capecitabine, and Celecoxib with Concurrent Radiation for Newly Diagnosed Resectable Rectal Cancer

Abstract

Lessons Learned. Colorectal cancers exhibit a high level of cyclooxygenase‐2 (COX‐2) expression with strong preclinical rationale for improved clinical outcomes with COX‐2 inhibition. Celecoxib is a COX‐2 inhibitor and we have shown that it can be safely combined with capecitabine and oxaliplatin as part of neoadjuvant treatment with radiation therapy (RT) in rectal cancer.There was a significant improvement in skin toxicity with this combination as compared with historical data. Considering the field has moved on to single‐agent capecitabine, we believe future trials with capecitabine and celecoxib hold potential.Background.Improved survival is seen among patients with rectal cancer who achieve pathologic complete response (pCR) after neoadjuvant therapy. Cyclooxygenase‐2 (COX‐2) expression is increased in gastrointestinal malignancies and it may serve as a target to enhance pathologic response. A trial combining chemoradiation and COX‐2 inhibition was conducted to evaluate the pCR rate, surgical outcomes, survival, and treatment toxicity.Methods.Patients with resectable (T3‐4, N1‐2) rectal cancer within 12 cm of the anal verge were included in this phase II clinical trial. The neoadjuvant treatment consisted of capecitabine 850 mg/m2 b.i.d. Monday through Friday for 5 weeks, weekly oxaliplatin 50 mg/m2 intravenous (IV), celecoxib 200 mg b.i.d. daily, along with concurrent 45 gray radiation therapy in 25 fractions.Results.Thirty‐two patients were included in the final analysis. The primary endpoint was pCR: 31% (95% confidence interval [CI]: 16%–50%). Secondary endpoints were surgical downstaging (SD): 75% (95% CI: 57%–89%) and sphincter‐sparing surgery (SSS): 56% (95% CI: 38%–74%). Common grade >3 toxicities were diarrhea and abnormal liver function tests (9% each). Grade 0 and 1 toxicities included radiation dermatitis (59% and 34%, respectively) and proctitis (63% and 28%, respectively). At 3 years, disease‐free survival and overall survival (OS) were 84% (95% CI: 65%–93%) and 94% (95% CI: 77%–98%), respectively.Conclusion.Chemoradiation with celecoxib in rectal cancer was well tolerated and demonstrated high rates of pCR, SD, and SSS. Improvement in skin toxicity (34% grade 1 and no grade 3/4) as compared with historical results (43%–78% grade 3/4) seems to be a significant improvement with addition of celecoxib to neoadjuvant chemotherapy.

The role of celecoxib for colorectal cancer treatment: a systematic review

“…Studies have suggested that the COX-inhibitor was a promising radiosensitizer, which could synergize with radiotherapy in the anti-tumor field (17,30,31,34).…”

“…Among the 12 included studies, 5 studies were RCTs (26-30), whereas the other 7 UCTs were conducted using single-arm design (31)(32)(33)(34)(35)(36)(37). Every participant was diagnosed with advanced unresectable or resectable CSC tumors.…”

Abnormal Liver Function Induced by Space-Occupying Lesions Is Associated with Unfavorable Oncologic Outcome in Patients with Colorectal Cancer Liver Metastases

“…The prognosis for metastatic CRC has significantly improved in the past 10–15 years, with more effective surgical approaches and efficacious chemotherapy regimens making it possible for patients to undergo surgical resection [ 3 ]. Even though the vast majority of metastatic CRC patients (80%–90%) present with unresectable disease, modern combination chemotherapy results in a median survival duration of roughly 20 months [ 4 – 6 ]. However, evaluating the prognosis of patients with CRC liver metastasis (CRLM) is still challenging, and the results will influence treatment strategies.…”

Synchronous Gastrointestinal Tumor and Abdominal Aortic Aneurysm or Dissection Treated with Endovascular Aneurysm Repair Followed by Tumor Resection

“…In the absence of such level of evidence, the management of gastrointestinal tumor has evolved into a multidisciplinary effort that requires chemotherapy, radiation, and surgical oncologists to elucidate a sound clinical treatment plan [18]. In order to reduce the probability of recurrence and to improve overall survival, preoperative chemoradiation and then radical excision is currently the standard of care for locally advanced stages of rectal cancer [19, 20].…”