Testing a Drug Combination with Fluorouracil, Irinotecan, Oxaliplatin, and Folinic Acid Plus Radiation Therapy for Patients with Advanced Rectal Cancer

Induction chemotherapy treatment

The first phase of treatment involves receiving a combination of chemotherapy medications through infusion, which means the medications will be delivered directly into a vein over a period of time.

Depending on the treatment group assigned, one of two chemotherapy combinations will be administered: either FOLFOXIRI or CAPOX/FOLFOX.

The FOLFOXIRI regimen includes four active substances: fluorouracil, irinotecan hydrochloride trihydrate, oxaliplatin, and folinic acid. All of these medications are given as infusions.

The CAPOX/FOLFOX regimen includes: oxaliplatin, fluorouracil, and folinic acid, also administered as infusions.

This chemotherapy phase is given in cycles, with each cycle lasting a specific number of days. The exact number of cycles, dosage amounts, and duration will be determined by the treating oncologist based on individual response and tolerance.

During this phase, regular monitoring will occur to check for any side effects or complications. Any side effects of grade 2 or higher, or blood-related side effects of grade 3 or higher, will be recorded.

Blood tests and other assessments will be performed to monitor how the body is responding to the treatment.

If side effects occur, the dose of medication may need to be reduced or adjusted. Any changes to the treatment plan will be documented and explained.

Quality of life questionnaires will be completed after this treatment phase to assess overall well-being.

Assessment after induction chemotherapy

After completing the chemotherapy cycles, imaging scans will be performed to evaluate how the tumor has responded to treatment.

An MRI scan (magnetic resonance imaging) will be used to create detailed images of the affected area. This scan uses magnetic fields and radio waves to produce pictures of the inside of the body.

A radiologist will review the scan images according to standardized procedures and document the findings in the medical file.

This assessment helps determine the next steps in the treatment plan.

Chemoradiotherapy treatment

The next phase combines chemotherapy with radiotherapy, which uses high-energy rays to target and destroy cancer cells.

The chemotherapy during this phase will be administered alongside the radiation treatments.

The specific chemotherapy medication used during this phase may include capecitabine or Teysuno, which are taken by mouth, or other infusion-based medications depending on the treatment plan.

Radiotherapy will be delivered in multiple sessions, typically on a daily basis over several weeks. Each session lasts only a few minutes.

During this phase, regular monitoring will occur to check for any side effects. Any side effects of grade 2 or higher, or blood-related side effects of grade 3 or higher, will be recorded.

If side effects occur, adjustments to the chemotherapy dose or radiation dose may be necessary.

Quality of life questionnaires will be completed after this treatment phase.

Assessment after chemoradiotherapy

Following the completion of chemoradiotherapy, another series of assessments will be performed to evaluate the tumor response.

An MRI scan will be performed to create detailed images of the treated area.

An endoscopic evaluation will be conducted, which involves inserting a thin, flexible tube with a camera into the rectum to directly visualize the treatment area.

A radiologist will review the MRI images, and the findings will be documented in the medical file.

The combined results from the MRI and endoscopy will help determine whether a complete clinical response has been achieved, meaning no visible tumor tissue remains.

Based on these results, a decision will be made regarding the next step: either proceeding to surgery or entering a monitoring approach without immediate surgery.

Treatment decision: surgery or watch-and-wait approach

Based on the assessment results, one of two paths will be followed.

If surgery is recommended, the procedure will involve removal of the affected portion of the rectum and surrounding tissue. This is known as TME surgery (total mesorectal excision).

The surgical approach and specific technique will be determined by the surgeon based on individual circumstances.

In some cases, intraoperative radiotherapy may be administered during the surgery, which means radiation is delivered directly to the treatment area while in the operating room.

If a complete clinical response has been achieved and certain criteria are met, a watch-and-wait approach may be offered instead of immediate surgery. This means close monitoring without surgery as long as no tumor growth is detected.

The decision between surgery and watch-and-wait will be made in consultation with the medical team based on the individual response to treatment.

Post-treatment monitoring (if surgery was performed)

After surgery, recovery will be monitored for any complications for up to three months.

Any complications will be graded using the Clavien-Dindo grading system, which classifies complications by their severity, and recorded in the medical file.

Once the surgical specimen is removed, it will be examined by a pathologist to determine the extent of tumor response to treatment.

The pathologist will assess whether a pathological complete response has been achieved, meaning no cancer cells are found in the removed tissue.

The pathologist will also assign a Mandard score, which grades the degree of tumor regression on a scale.

Quality of life questionnaires will be completed at three months after surgery.

Regular follow-up appointments will be scheduled to monitor for any signs of cancer recurrence.

Long-term follow-up monitoring

Regular follow-up will continue for several years to monitor for any signs of cancer returning or spreading.

Follow-up assessments will include imaging scans and clinical examinations at scheduled intervals.

If the watch-and-wait approach was chosen, MRI scans and endoscopic examinations will be performed regularly to ensure no tumor regrowth occurs.

A specific assessment will be conducted at one year after completing chemoradiotherapy to confirm whether a sustained complete clinical response has been maintained.

Quality of life questionnaires will be completed at 12 months and 24 months after surgery or after entering the watch-and-wait approach.

Follow-up will continue at three years and five years to assess long-term outcomes.

Any signs of local recurrence, which means cancer returning in the same area, or distant metastasis, which means cancer spreading to other parts of the body, will be evaluated through imaging or tissue examination.

The goal of long-term follow-up is to detect any changes early and determine the overall success of the treatment approach.