Chemotherapy Alone for Patients With Stage II/III Rectal Cancer Undergoing Radical Surgery

Abstract

Purpose. The purpose of this prospective pilot study was to determine the efficacy of preoperative chemotherapy with six cycles of FOLFOX 6 (without radiation therapy) followed by radical surgery followed by six additional cycles of FOLFOX 6 for patients with stage II/III rectal cancer. Patients and Methods. From January 2010 to January 2014, patients with locally advanced rectal cancer who met the eligibility criteria were enrolled in this study. Patients received FOLFOX 6 chemotherapy comprising oxaliplatin and leucovorin calcium i.v. over 2 hours on day 1, then bolus, and then continuous fluorouracil i.v. over 46 hours on days 1 and 2. Treatment was repeated every 14 days for 6 courses followed by radical surgery followed by additional 6 cycles of FOLFOX 6. Results. In total, 45 patients were enrolled in this study. In the preoperative re-evaluation, the overall response rate was 68.8% (clinical complete response was 4.4%, and the partial response was 64.4%). There were 14 cases (31.2%) of stable disease. No patients had progressive disease. Postoperatively, the pathologic complete response rate was 8 of 45 (17.8%; 95% confidence interval [CI]: 8.9%-28.9%). The median follow-up was 29 months (range 9-54 months). The actuarial 3-year overall survival and disease-free survival rates for all patients were 80.8% (standard error, 1.877; 95% CI: 69.3%-92.3%) and 67.9% (standard error, 2.319; 95% CI: 54.3%-81.5%), respectively. Conclusion. Neoadjuvant chemotherapy (FOLFOX) without radiotherapy is active and safe but cannot be considered a standard of care until the results of prospective randomized phase III trials are available. The Oncologist 2015; 20:752-757 Implications for Practice: Neoadjuvant radiotherapy of rectal cancer represents the current standard of care. However, its use is also associated with short-term toxicity and long-term morbidity.With the increasing use of total mesorectal resection resulting in better local control and advances in systemic therapy for colorectal cancer, this study highlights the question of whether radiation is a necessary component of neoadjuvant therapy for all patients with rectal cancer or whether select patients could be spared the additional toxicities and inconvenience of radiotherapy. This study suggests that neoadjuvant FOLFOX without radiotherapy is active and safe, but it could not be considered a standard of care till now.

Feasibility of Neoadjuvant FOLFOX Therapy Without Radiotherapy for Baseline Resectable Rectal Cancer

“…In this study, the response rate was 56.7% and the pCR rate was 6.7%. Previous studies on oxaliplatin-based regimens without a molecular-target drug revealed a pCR rate of 6.6%-12.2% (14,17,18,24). The pCR rate might increase with the addition of a molecular-target drug.…”

“…R0 resection rate after NAC was 100% among patients who were judged to be capable of undergoing radical excision at baseline. Previous reports also showed the R0 resection rates of NAC for cT3-4 (except T4b) were high, ranging from 98.3% to 100% (11)(12)(13)(14). An important problem inherent in preoperative treatment is that surgical curability may be impaired by tumour growth during the treatment.…”

“…However, the relationship between histological response and prognosis in NAC has not been clarified, though many reports on NACRT showed pCR and good histological response were associated with a good prognosis (25)(26)(27)(28). AlGizawy et al (14) reported on NAC involving XELOX plus bevacizumab and mentioned that this strategy had a high pCR of 20% and a 2-year DFS rate of 70%. On the other hand, our strategy had a low pCR of 6.7% and a 3-year DFS rate of 77.5%.…”

Response to neoadjuvant treatment in rectal cancer surgery

“…Other chemotherapeutic agents such as irinotecan or monoclonal antibodies such as bevacizumab have not been shown to have this effect either (45). The side-effects of 5-FU based chemotherapy as single therapy or in combination with other therapies in the neoadjuvant setting are usually well tolerated with less than 5% having severe toxic reactions because of the short-term exposure (46). Current treatment schedules include nearly 6 weeks of neoadjuvant chemo radiation, 6-8 weeks of recovery prior to surgery, and another 4 weeks of recovery prior to consideration for adjuvant therapy.…”

“…Thus an alternative could be neoadjuvant chemotherapy alone. There is limited experience of chemotherapy as single treatment modality but initial reports are encouraging in terms of both down-staging and outcome but further research with long-term follow-up is needed and initiated (43,46,47). …”