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خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : -41 مورد

Systemic therapy regimens for rectal cancer in both the adjuvant* and neoadjuvant setting: Concomitant chemoradiotherapy with capecitabine[1]

Systemic therapy regimens for rectal cancer in both the adjuvant* and neoadjuvant setting: Concomitant chemoradiotherapy with capecitabine[1]
Cycle length: 5 to 6 weeks (chemoradiotherapy).
Drug Dose and route Administration Given on days
CapecitabineΔ 825 mg/m2 by mouth Twice daily; total daily dose 1650 mg/m2. Swallow whole with water within 30 minutes after a meal, with each dose as close to 12 hours apart as possible. Do not cut or crush tablets.◊ Daily, 5 days per week (Monday through Friday), during entire 5- to 6-week course of radiation beginning on week 1
Radiotherapy (50.4 Gy) 1.8 Gy for five days a week Begin within 24 hours of beginning chemotherapy. Beginning week 1 and continuing to week 6
Pretreatment considerations:
Emesis risk
  • LOW.
  • Refer to UpToDate topics on prevention of chemotherapy-induced nausea and vomiting in adults.
Infection prophylaxis
  • Primary prophylaxis with G-CSF is not indicated.
  • Refer to UpToDate topics on prophylaxis of infection during chemotherapy-induced neutropenia in high-risk adults.
Dose adjustment for baseline liver or kidney dysfunction
  • Lower starting doses of capecitabine may be needed for kidney impairment.[2]
  • Refer to UpToDate topics on chemotherapy nephrotoxicity and dose modification in patients with kidney insufficiency, conventional cytotoxic agents.
Monitoring parameters:
  • CBC with differential and platelet count weekly during chemoradiotherapy.
  • Assess electrolytes and liver and kidney function weekly during chemoradiotherapy.
  • Monitor for diarrhea, stomatitis, and cutaneous toxicity (palmar-plantar erythrodysesthesias) during treatment.
  • Refer to UpToDate topics on cutaneous side effects of conventional chemotherapy agents.
  • Doses of phenytoin and of coumarin-derivative anticoagulants may need to be reduced when either drug is administered concomitantly with capecitabine. More frequent anticoagulant response (INR or prothrombin time) monitoring is necessary for patients receiving concomitant capecitabine and oral coumarin-derivative anticoagulant therapy.
  • Cardiotoxicity observed with capecitabine includes myocardial infarction/ischemia, angina, dysrhythmias, cardiac arrest, cardiac failure, sudden death, electrocardiographic changes, and cardiomyopathy. These adverse reactions may be more common in patients with a prior history of coronary artery disease.
  • Refer to UpToDate topics on cardiotoxicity of cancer chemotherapy agents other than anthracyclines, HER2-targeted agents, and fluoropyrimidines.
Suggested dose modifications for toxicity:
Myelotoxicity
  • For neutrophils <1200/microL during therapy, hold capecitabine until ≥1200/microL, then reduce capecitabine to 620 mg/m2 twice daily; if recurs, hold capecitabine until neutrophils ≥1200/microL, then reduce capecitabine to 465 mg/m2 twice daily.[3] For platelet count <75,000/microL during therapy, hold capecitabine until ≥75,000/microL, and reduce subsequent doses of capecitabine to 620 mg/m2 twice daily; if recurs, hold capecitabine until platelet count ≥75,000/microL, and reduce subsequent capecitabine doses to 465 mg/m2 twice daily. If recovery takes >2 weeks, discontinue chemotherapy. For febrile neutropenia or infection with grade 3 or 4 neutropenia, hold chemotherapy until clinical resolution then resume at reduced dose of capecitabine (620 mg/m2 twice daily).
Gastrointestinal toxicity
  • Hold capecitabine for grade 2 vomiting (despite antiemetics) or grade 2 or 3 diarrhea or mucositis, and delay reinitiation until ≤grade 1; for first occurrence, reduce capecitabine dose to 620 mg/m2 twice daily; for second occurrence, reduce capecitabine to 465 mg/m2 twice daily; for third occurrence, or any grade 4 diarrhea, or grade 3 or 4 vomiting, or if recovery takes >2 weeks, discontinue capecitabine.[3]
  • NOTE: Severe diarrhea, mucositis, and myelosuppression after capecitabine should prompt evaluation for DPD deficiency.
  • Refer to UpToDate topics on enterotoxicity of chemotherapeutic agents.
Hand-foot syndrome
  • For grade 2 or 3 hand-foot syndrome, hold capecitabine until ≤grade 1.[3] Resume capecitabine at 620 mg/m2 twice daily. For second occurrence, hold capecitabine until ≤grade 1, and resume capecitabine at 465 mg/m2 twice daily. For third occurrence or any grade 4 toxicity, discontinue capecitabine.
Hepatotoxicity
  • For grade 2 transaminase elevation during therapy, hold capecitabine until ≤grade 1; resume capecitabine at 620 mg/m2 twice daily.[3] Patients with grade 3 or 4 hyperbilirubinemia may resume capecitabine once toxicity has reduced to grade ≤2, but at a reduced dose. 
Other clinically significant adverse events
  • For other grade 3 adverse events, hold therapy until ≤grade 1, then resume at a lower dose (620 mg/m2 twice daily); discontinue chemotherapy for grade 4.[3]
If there is a change in body weight of at least 10%, doses should be recalculated.
This table is provided as an example of how to administer this regimen; there may be other acceptable methods. This regimen must be administered by a clinician trained in the use of chemotherapy, who should use independent medical judgment in the context of individual circumstances to make adjustments, as necessary.

AST: aspartate aminotransferase; CBC: complete blood count; DPD: dihydropyrimidine dehydrogenase; G-CSF: granulocyte colony stimulating factor; Gy: gray; INR: international normalized ratio.

* In the adjuvant setting, concomitant capecitabine-based chemoradiotherapy is generally combined with four to six months of fluoropyrimidine-based adjuvant chemotherapy. Chemotherapy options include capecitabine alone, short-term infusional fluorouracil plus leucovorin with or without oxaliplatin, or weekly fluorouracil plus leucovorin, as used for adjuvant treatment of colon cancer. The optimal sequencing has not been established, but the authors generally gave all the radiotherapy first or last, but not in between courses of chemotherapy. Refer to UpToDate topics on adjuvant therapy for resected rectal adenocarcinoma in patients not receiving neoadjuvant therapy.

¶ In the neoadjuvant setting, concomitant chemoradiotherapy is generally given upfront prior to surgical resection. Following surgery, adjuvant chemotherapy for four to six months may be recommended. Chemotherapy options include capecitabine alone, short-term infusional fluorouracil plus leucovorin with or without oxaliplatin, or weekly fluorouracil plus leucovorin, as used for adjuvant treatment of colon cancer. Refer to UpToDate topics on neoadjuvant chemoradiotherapy, radiotherapy, and chemotherapy for rectal adenocarcinoma.

Δ No capecitabine dose has been shown to be safe in patients with complete DPD deficiency, and data are insufficient to recommend a dose in patients with partial DPD activity.

◊ Extemporaneous compounding of liquid dosage forms has been recommended, but intravenous therapies may be more appropriate for patients with significant swallowing difficulty.

References:
  1. O'Connell MJ, Colangelo LH, Beart RW, et al. Capecitabine and oxaliplatin in the preoperative multimodality treatment of rectal cancer: Surgical end points from National Surgical Adjuvant Breast and Bowel Project trial R-04. J Clin Oncol 2014; 32:1927.
  2. Capecitabine. United States Prescribing Information. US National Library of Medicine. (Available online at https://dailymed.nlm.nih.gov/dailymed/index.cfm, accessed on  February 19, 2024).
  3. Dose modifications per NSABP protocol R-04. US National Library of Medicine. (Available online at https://clinicaltrials.gov/study/NCT00058474, accessed on February 19, 2024).
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