Maintaining High Quality of Life, Good Performance Status in Refractory Colorectal Cancer
Welcome to this Clinical Case Series learning module!
Here's how it works:
- Read these 3 case studies on the AP role in managing third-line metastatic CRC in patients.
- Answer the poll next to each case to see how your colleagues are managing these patients. You'll see results in real time.
- Continue your learning by watching a recording of a webinar presented by Tammy Triglianos, DNP, ANP-BC, AOCNP
Understanding Dosing for Combination Trifluridine and Tipiracil
Clinical Pearl: Dosing of combination trifluridine and tipiracil is based on the patients body surface area, and the total dose can be split among two oral doses.
A 49-year-old man presented to the ED with complaints of lower abdominal pain, nausea, and vomiting. He was found to have a hemoglobin level of 7.6 g/dL. CT of the abdomen and pelvis showed a right-sided bladder mass with extension into the right lower quadrant and suspected connection with the distal ileum, as well as small bowel obstruction with transition point, suspicious for genitourinary versus gastrointestinal primary malignancy. He was taken to the operating room for diagnostic laparoscopy and enteroenteric bypass, with diverting ileostomy. Operative findings confirmed carcinomatosis. The final pathology report showed moderately differentiated adenocarcinoma consistent with a primary colorectal cancer (CK20 and CDX2 positive, CK7 and GATA3 negative).
The patient was initially treated with folinic acid, fluorouracil, oxaliplatin, and irinotecan (FOLFOXIRI); addition of bevacizumab was deferred due to the recent surgery and a complex primary tumor, with extensive local involvement and fistulization. He was treated to maximum response; shortly after the completion, he returned to the OR for right hemicolectomy and partial cystectomy (without evidence of carcinomatosis). The final pathology report revealed poorly differentiated adenocarcinoma of the cecum, direct invasion into the bladder, lymph node involvement in four nodes (ypT4bN2a), microsatellite stability (MSS), and a KRAS mutation. A treatment holiday of approximately 6 months was recommended, after which a follow-up CT showed disease progression with increased carcinomatosis. Chemotherapy was restarted, recycling multiple lines of prior standard-of-care therapy over an 8-month period. After disease progression through these standard therapies, he was considered to have refractory disease.
At this point, treatment options were discussed with the patient and included (1) combination trifluridine and tipiracil plus bevacizumab, (2) regorafenib, or (3) best supportive care. Trifluridine and tipiracil plus bevacizumab was selected because this combination has shown efficacy for progression-free survival and overall survival.1-4 The side-effect profile was also taken into consideration. Of note, bevacizumab was no longer contraindicated given that the complex primary tumor had been removed and the fistulization had resolved with surgery.
Dosing of combination trifluridine and tipiracil was 35 mg/m2 twice daily on Days 1-5 and Days 8‑12 of each 28-day cycle. The patient’s body surface area (BSA) was 2.0 m2, which equated to 70 mg twice daily of trifluridine and tipiracil on Days 1-5 and on Days 8-12 of each 28-day cycle. This combination comes in two oral doses: 15 mg and 20 mg.
| Patient Instructions for Combination Trifluridine and Tipiracil |
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The first cycle of combination trifluridine and tipiracil was well tolerated. Side effects included fatigue and mild nausea controlled with ondansetron. After 2 months of therapy, the first restaging scans showed stable disease.
Initiation of Cycle 3 was delayed by 1 week due to grade 2 neutropenia (absolute neutrophil count [ANC] of 1.0 x 109/L). The ANC recovered to 3.0 x 109/L, and therapy resumed. No growth factor support was administered with therapy, as dose holds or dose reductions are generally used to manage neutropenia.
Prior to starting Cycle 4, the ANC dropped to 0.7 x 109/L. Treatment was held for 1 week, but the ANC was persistently low, so treatment was held for an additional week. The ANC increased to 2.6 x 109/L, and treatment was restarted at a reduced dose because of the Cycle 4 initiation delay of more than 1 week. Due to weight loss (BSA 1.9 m2), the dose was recalculated using the recommended dose reduction (decrease 5 mg/m2/dose) to 30 mg/m2 (55 mg twice daily).
After 4 months of therapy, a restaging scan showed essentially stable disease with a minor (just a few millimeters) increase in peritoneal disease. The advanced practitioner and the patient discussed the results and decided to maintain treatment.
References
- Kotani D, Kuboki Y, Horassawa S, et al. Retrospective cohort study of trifluridine/tipiracil (TAS-102) plus bevacizumab versus trifluridine/tipiracil monotherapy for metastatic colorectal cancer. BMC Cancer. 2019;19:1253.
- Matsuhashi N, Takahashi T, Fujii H, et al. Combination chemotherapy with TAS-102 plus bevacizumab in salvage-line treatment of metastatic colorectal cancer: A single-center, retrospective study examining the prognostic value of the modified Glasgow Prognostic Score in salvage-line therapy of metastatic colorectal cancer. Mol Clin Oncol. 2019;11:390-396.
- Pfeiffer P, Yilmaz M, Möller S, et al. Bevacizumab improves efficacy of trifluridine/tipiracil (TAS-102) in patients with chemorefractory metastatic colorectal cancer: A Danish randomized trial. Ann Oncol. 2019;30 Suppl 4:iv130-iv131.
- Prager G W, Taieb J, Fakih M, et al. SUNLIGHT (2023). Trifluridine-tipiracil and bevacizumab in refractory metastatic colorectal cancer. N Engl J Med. 2023:388:1657-1667.
Maintaining Performance Status Despite Disease Progression
Clinical Pearl: Dosing plans, including reductions and delays, should be altered for neutropenia.
A 62-year-old man has a history of cecal mass on screening colonoscopy and is initially diagnosed with a stage IIIB (pT4aN1bM0) cecal adenocarcinoma, microsatellite stability (MSS), after a right hemicolectomy. He subsequently received adjuvant folinic acid, fluorouracil, and oxaliplatin (FOLFOX) for 6 months. A year after completing therapy, he was found to have radiographic recurrence with new liver metastases, and a biopsy confirmed microsatellite stable, KRAS wild type adenocarcinoma. The patient initially planned to undergo hepatectomy, but he was found to have numerous peritoneal implants at the time of surgery. He was then started on systemic therapy and eventually underwent cytoreductive surgery (CRS)/hyperthermic intraperitoneal chemotherapy (HIPEC). Unfortunately, radiographic recurrence with multifocal peritoneal implants was found 6 months later. Systemic therapy was restarted, and the patient cycled through first- and second-line therapies.
At that point, the patient was considered to have refractory disease. The care team discussed treatment options with him, and the advanced practitioner (AP) presented the following options: (1) recycle FOLFOX, (2) combination trifluridine and tipiracil with bevacizumab, or (3) regorafenib. Given the persistent and significant neuropathy the patient experienced from prior oxaliplatin therapy, through shared decision-making, his choice was to pursue combination trifluridine and tipiracil with bevacizumab.
The patient’s body surface area (BSA) was 1.6 m2, so combination trifluridine and tipiracil was initiated at 60 mg (35 mg/m2) twice daily on Days 1-5 and 8-12 of a 28-day cycle. The patient experienced fatigue and nausea during the first two cycles. After Cycle 2 of therapy, he developed neutropenia. The dose was reduced to 60 mg (30 mg/m2 twice daily) in the morning and 40 mg in the evening. This dosing plan was further adjusted based on the pill size that the patient already had.
Multiple dose delays were necessary because of the neutropenia. Many discussions occurred between the AP and the patient regarding his overall goals of care and his concern over delays in treatment related to neutropenia. He frequently expressed the desire to pursue options to prolong his life.
After 8 months of therapy, mild disease progression < 20% was found. This did not meet the RECIST definition of at least 20% of the sum of the target lesion(s) for progression;1 therefore, the AP and patient decided to maintain the current treatment plan.
Reference
- Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228-247.
Progressive Symptoms Lead to Poor Quality of Life, Treatment Discontinuation
Clinical Pearl: Patient goals and symptoms should inform all communication with advanced practitioners, especially shared decision-making conversations.
A 53-year-old woman was initially diagnosed with stage IV colon cancer, with metastatic disease to the liver and peritoneum, microsatellite stability (MSS), and a KRAS mutation. She was started on folinic acid, fluorouracil, oxaliplatin, and irinotecan (FOLFOXIRI) plus bevacizumab; oxaliplatin was held after 6 months of therapy due to progressive neuropathy and disease control. The patient was eventually transitioned to maintenance therapy with folinic acid, fluorouracil, and bevacizumab. Almost 3 years after her initial diagnosis, she experienced disease progression in the peritoneum and was transitioned back to irinotecan and bevacizumab. She had declined cytoreductive surgery/hyperthermic intraperitoneal chemotherapy (HIPEC) due to concern about surgical complications and a potential risk of a decline in her quality of life. Approximately 1 year later, the patient experienced disease progression again.
After a discussion with her care team, treatment was switched to combination trifluridine and tipiracil, administered as 70 mg (35 mg/m2) twice daily on Days 1-5 and 8-12 of a 28-day cycle, plus bevacizumab. Cycle 1 was complicated by grade 2 neutropenia; therefore, Cycle 2 was delayed; Cycle 2 was complicated by grade 4 neutropenia, grade 2 thrombocytopenia, and grade 3 anemia, delaying the start of Cycle 3. Dose modification alone would likely not be sufficient because it took 2 weeks to recover white blood cell counts; therefore, the dosing and schedule were changed to 50 mg twice daily on Days 1-5 every 2 weeks.1
The first restaging scan showed mostly stable disease, with only a few millimeters of change in the peritoneal nodule, so the treatment plan was maintained. Two months later (after a total of 4 months of therapy), she experienced clinical progression with significant nausea, early satiety, and progressive fatigue. On physical exam, she was found to have new ascites. Restaging scans showed significant progression in peritoneal disease, with new ascites.
Throughout her treatment course, the advanced practitioner and the patient had multiple shared decision-making conversations. The decisions regarding therapeutic selection resulted from those discussions, with high quality of life being the main goal.
Reference
- Satake H, Kato T, Oba K, et al. Phase Ib/II study of biweekly TAS-102 in combination with bevacizumab for patients with metastatic colorectal cancer refractory to standard therapies (BiTS Study). Oncologist. 2020;25:e1855-e1863.
Meet the Faculty
Tammy Triglianos
DNP, ANP-BC, AOCNP
Adult Oncology Nurse Practitioner
UNC Lineberger Comprehensive Cancer Center
Tammy Triglianos, DNP, ANP-BC, AOCNP is an Adult Oncology Nurse Practitioner at the UNC Lineberger Comprehensive Cancer Center and an Assistant Professor in the UNC School of Nursing. She received her Master’s in Nursing from Columbia University and her Doctorate in Nursing Practice from UNC. Dr. Triglianos's clinical focus is on gastrointestinal medical oncology and she recently established an Undiagnosed Cancer clinic. She serves on the Education Committee of APSHO, is a member of the ASCO APP Task Force, and co-chairs the Leadership & Mentorship committee of her local ONS chapter.
Let us know what you'd like to learn more about at jadpro-editor@broadcastmed.com