Results of phase II trial of intensified neoadjuvant treatment with interdigitating radiotherapy and chemotherapy with oxaliplatin, 5-fluorouracil and folinic acid in patients with locally advanced rectal cancer (PROARCT trial)

doi:10.1016/j.radonc.2020.10.012

Radiotherapy and Oncology

Volume 155, February 2021, Pages 27-32

https://doi.org/10.1016/j.radonc.2020.10.012 Get rights and content

Highlights

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Majority of cohort (95%) completed intensified neoadjuvant treatment with no treatment break.
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Neoadjuvant treatment with interdigitating chemotherapy and radiotherapy is feasible.
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Advantages of upfront chemotherapy include reduced treatment time and improved compliance.

Abstract

Background and purpose

The chemotherapy exposure during chemoradiotherapy for rectal cancer is adequate for radiosensitization but suboptimal for treatment of distant micrometastasis. This study aimed to determine tolerability, dose intensity, response, and toxicity of a novel intensified neoadjuvant treatment approach.

Materials and Methods

Eligible patients were MRI-staged T3-4NxM0 rectal adenocarcinoma. Treatment consisted of FOLFOX chemotherapy given in weeks 1, 6, and 11 with pelvic radiotherapy (25.2 Gy in 3 weeks in 1.8 Gy/fraction with oxaliplatin and 5-FU continuous infusion) given in weeks 3–5, and weeks 8–10. Surgery was performed 4–6 weeks later. The primary endpoint was tolerability defined as the percentage of patients who were able to complete the planned treatment course. Survival rates were estimated using the Kaplan-Meier method.

Results

Median age of the 40 patients was 61.5 years. Rectal MRI-stage was T3 in 88%. Overall, 95% completed the regimen. All patients received 50.4 Gy. Relative dose intensity (≥75%) was 92% and 98% for oxaliplatin and 5-FU, respectively. High grade toxicities included neutropenia (25% grade 3; 7.5% grade 4) and diarrhoea (10%). Pathologic CR rate was 20%. Median follow-up was 54 months. The 5-year overall survival, freedom from relapse, locoregional control, and freedom from distant metastasis of the cohort was 82%, 72%, 97% and 72%.

Conclusions

Delivery of intensified neoadjuvant treatment with interdigitating chemotherapy and radiotherapy is feasible with no increase in acute perioperative complications. A larger prospective study is required to further evaluate the potential survival benefit of this design.

Section snippets

Materials and methods

The protocol was approved by the trial sponsor and ethics committees of all participating centres. Written informed consent was obtained from each patient. This trial was performed under the auspices of Trans-Tasman Radiation Oncology Group (TROG). ClinicalTrials.gov Identifier: NCT01013805.

Results

Forty-one patients were recruited between April 2010 and July 2012. The last patient completed preoperative in October 2012 and surgery in November 2012. One patient was removed from the trial by the investigator after the first week as the patient was non-compliant with the trial treatment plan, resulting in a total of 40 analysable patients. The patient characteristics are summarised in Table 1.

Thirty-eight patients (95%; 80% CI: 87–99%) completed treatment protocol without any treatment

Discussion

This study investigates the feasibility and safety of an INT with interdigitating FOLFOX and chemoradiotherapy for locally advanced rectal cancer. This treatment regimen was designed to address the increasingly important role of chemotherapy to eradicate micrometastatic disease, a drawback of the current standard preoperative chemoradiotherapy. Our study demonstrated that this treatment schedule has high compliance rate with no increase in post-operative complications.

The current standard of

Funding

This trial was supported by Cancer Australia Priority-driven Collaborative Cancer Research Scheme, and Commonwealth Department of Health and Ageing Strengthening Cancer Care Program.

Conflict of interest

None.

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Original ArticleResults of phase II trial of intensified neoadjuvant treatment with interdigitating radiotherapy and chemotherapy with oxaliplatin, 5-fluorouracil and folinic acid in patients with locally advanced rectal cancer (PROARCT trial)

Highlights

Abstract

Background and purpose

Materials and Methods

Results

Conclusions

Section snippets

Materials and methods

Results

Discussion

Funding

Conflict of interest

Lancet Oncol

Int J Radiat Oncol Biol Phys

Lancet Oncol

Promising results of a cooperative group phase II trial of preoperative chemoradiation for locally advanced rectal cancer (TROG 9801)

Dis Colon Rectum

Improving adjuvant therapy for rectal cancer by combining protracted-infusion fluorouracil with radiation therapy after curative surgery

N Engl J Med

Preoperative versus postoperative chemoradiotherapy for rectal cancer

N Engl J Med

Randomized trial of short-course radiotherapy versus long-course chemoradiation comparing rates of local recurrence in patients with T3 rectal cancer: Trans-Tasman Radiation Oncology Group trial 01.04

J Clin Oncol

Phase II trial evaluating the feasibility of interdigitating folfox with chemoradiotherapy in locally advanced and metastatic rectal cancer

Br J Cancer

Original Article
Results of phase II trial of intensified neoadjuvant treatment with interdigitating radiotherapy and chemotherapy with oxaliplatin, 5-fluorouracil and folinic acid in patients with locally advanced rectal cancer (PROARCT trial)