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Weekly carboplatin and paclitaxel chemotherapy with concurrent radiotherapy for esophageal and esophagogastric junction (EGJ) cancer[1]

Weekly carboplatin and paclitaxel chemotherapy with concurrent radiotherapy for esophageal and esophagogastric junction (EGJ) cancer[1]
Cycle length: Carboplatin and paclitaxel are each given weekly for five weeks with concurrent RT followed by surgery.
Drug Dose and route Administration Given on days
Paclitaxel 50 mg/m2 IV Dilute in 250 mL NS* and administer over one hour; special tubing needed. Days 1, 8, 15, 22, and 29
Carboplatin AUCΔ = 2 mg/mL × min IV Dilute in 250 mL NS* and administer over 30 minutes after paclitaxel. Days 1, 8, 15, 22, and 29
Pretreatment considerations:
Emesis risk
  • MODERATE (30 to 90% frequency of emesis). We recommend prophylaxis with a combination of a 5-HT3 receptor antagonist plus dexamethasone on days 1, 8, 15, 22, and 29, and with a 5-HT3 antagonist on days when radiation alone is given.
  • Refer to UpToDate topics on "Prevention and treatment of chemotherapy-induced nausea and vomiting in adults" and "Radiotherapy-induced nausea and vomiting: Prophylaxis and treatment".
Prophylaxis for infusion reactions
  • Premedicate with dexamethasone plus both an H1 and an H2 receptor antagonist prior to paclitaxel administration.
  • Refer to UpToDate topic on "Infusion reactions to systemic chemotherapy".
Vesicant/irritant properties
  • Carboplatin is an irritant. Paclitaxel can cause significant tissue damage; avoid extravasation.
  • Refer to UpToDate topic on "Extravasation injury from chemotherapy and other non-antineoplastic vesicants".
Infection prophylaxis
  • Primary prophylaxis with G-CSF is not justified (incidence of neutropenic fever <1%[1]).
  • Refer to UpToDate topic on "Use of granulocyte colony stimulating factors in adult patients with chemotherapy-induced neutropenia and conditions other than acute leukemia, myelodysplastic syndrome, and hematopoietic cell transplantation".
Dose adjustment for baseline liver or renal dysfunction
  • A lower starting dose of paclitaxel may be needed for liver impairment.[2] Carboplatin dose is calculated based upon renal function by use of the Calvert formula.Δ[3]
  • Refer to UpToDate topics on "Chemotherapy hepatotoxicity and dose modification in patients with liver disease: Conventional cytotoxic agents" and "Chemotherapy hepatotoxicity and dose modification in patients with liver disease: Molecularly targeted agents" and "Dosing of anticancer agents in adults".
Monitoring parameters:
  • CBC with differential and platelet count weekly during treatment.
  • Assess electrolytes, renal, and liver function weekly during treatment.
  • Assess changes in neurologic function weekly during treatment.
Suggested dose modifications for toxicity:
Myelotoxicity/neurologic toxicity
  • Weekly doses of paclitaxel and carboplatin should not be repeated unless the ANC is at least 1500/microL and the platelet count is at least 100,000/microL. Reduce paclitaxel dose by 20% for ANC <500/microL for a week or longer, or severe peripheral neuropathy.[2]
Renal toxicity
  • Alterations in renal function during therapy require a recalculation of the carboplatin dose.
  • Refer to UpToDate topic on "Dosing of anticancer agents in adults".
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.
RT: radiotherapy; IV: intravenous; NS: normal saline; AUC: area under the concentration × time curve; G-CSF: granulocyte colony stimulating factor; CBC: complete blood count; ANC: absolute neutrophil count; GFR: glomerular filtration rate; NCCN: National Comprehensive Cancer Network.
* Diluent solutions should not be modified without consulting a detailed reference due to potential incompatibility(ies).
¶ Paclitaxel can be administered in NS, D5W, or NS/D5W* at varying concentrations between 0.3 to 1.2 mg/mL. Use glass or polypropylene bottles or polypropylene or polyolefin plastic bags, and administer through a polyethylene-lined administration sets with a microporous membrane 0.22 microns or less.
Δ AUC is converted to a patient-specific carboplatin dose (in mg) according to renal function by using the Calvert formula: Total dose (mg) = (target AUC) × (GFR + 25). If using measured creatinine, limit the maximal GFR for the calculation to 125 mL/min. Refer to UpToDate topic on "Dosing of anticancer agents in adults".
References:
  1. Gaast AV, et al. Effect of preoperative concurrent chemoradiotherapy on survival of patients with resectable esophageal or esophagogastric cancer: Results from a multinational randomized phase III study (abstract 4004). J Clin Oncol 2010; 28:302s.
  2. Paclitaxel injection. United States Prescribing Information. US National Library of Medicine. (Available online at dailymed.nlm.nih.gov, accessed on October 29, 2019).
  3. Carboplatin injection. United States Prescribing Information. US National Library of Medicine. (Available online at dailymed.nlm.nih.gov, accessed on October 29, 2019).
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