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تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
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Chemotherapy regimens for advanced epithelial ovarian, uterine, or cervical cancer: Paclitaxel and carboplatin[1-3]

Chemotherapy regimens for advanced epithelial ovarian, uterine, or cervical cancer: Paclitaxel and carboplatin[1-3]
Cycle length: 21 days.
Total cycles: 6 (in first-line setting, or until disease progression or unacceptable toxicity).
Drug Dose and route Administration Given on days
Paclitaxel 175 mg/m2 IV Dilute in 1000 mL NS or D5W* and administer over three hours. Day 1
Carboplatin AUCΔ = 6◊ mg/mL per min IV Dilute in 250 mL NS or D5W* and administer over 30 minutes (administer after the completion of the paclitaxel infusion). Day 1
Pretreatment considerations:
Emesis risk
  • MODERATE (30 to 90% frequency of emesis).§
  • Refer to UpToDate topics on prevention of chemotherapy-induced nausea and vomiting in adults.
Dose adjustment for baseline liver or kidney dysfunction
  • Each carboplatin dose should be calculated based upon kidney function by use of the Calvert formula.Δ A lower starting dose of paclitaxel may be needed in patients with liver impairment.
  • Refer to UpToDate topics on chemotherapy hepatotoxicity and dose modification in patients with liver disease, conventional cytotoxic agents; chemotherapy hepatotoxicity and dose modification in patients with liver disease, molecularly targeted agents; and dosing of anticancer agents in adults.
Prophylaxis for infusion reactions
  • Paclitaxel may cause severe hypersensitivity reactions. Premedication regimen should include dexamethasone (either 20 mg orally 12 and 6 hours before, or 20 mg IV 30 minutes before drug administration) plus both an H1 (diphenhydramine 25 to 50 mg IV) and an H2 receptor antagonist (famotidine 20 mg IV) 30 to 60 minutes prior to paclitaxel administration.[4] Severe infusion reactions (eg, skin rash, flushing, dyspnea, urticaria, back pain, hypotension, chest pain, tachycardia) occur primarily during the first and second infusions, typically within the first hour after the start of the infusion. Further information on infusion reactions, including management, is available.
  • Carboplatin is also associated with infusion reactions. However, they usually occur after six cycles, and no specific premedication regimen is recommended. Further information on infusion reactions, including skin testing and desensitization, is available.
  • Refer to UpToDate topics on infusion reactions to systemic chemotherapy.
Vesicant/irritant properties
  • Paclitaxel can cause significant tissue damage; avoid extravasation.
  • Refer to UpToDate topics on extravasation injury from chemotherapy and other non-antineoplastic vesicants.
Monitoring parameters:
  • CBC with differential weekly during treatment.
  • Serum electrolytes and liver and kidney function tests prior to each treatment cycle.
  • Assess changes in neurologic function prior to each treatment cycle.
Suggested dose modifications for toxicity:
Myelotoxicity
  • Treatment with paclitaxel and carboplatin should be delayed until the ANC is >1500/microL and platelet count is >100,000/microL.[4,5] If a patient developed severe neutropenia (<500/microL) for a week or longer, or febrile neutropenia during the prior course, then the paclitaxel and carboplatin doses should be reduced by 20 to 25% for subsequent courses or initiation of hematopoietic growth factor support. Both the carboplatin and paclitaxel doses should be decreased by 25% in patients whose platelet count nadir is <25,000/microL for longer than five days.
Neurologic toxicity
  • For patients who develop severe neuropathy (grade 3 or 4) for a week or longer, then the dose of paclitaxel should be reduced by 20% for subsequent courses.[4]
Dose adjustment for liver or kidney dysfunction
  • Alterations in kidney function during therapy may require a recalculation of the carboplatin dose. Paclitaxel dose may need to be adjusted for hepatic impairment on day 1 of each cycle.
  • 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.
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.

ANC: absolute neutrophil count; AUC: area under the concentration × time curve; CBC: complete blood count; D5W: 5% dextrose in water; GFR: glomerular filtration rate; IV: intravenous; NCCN: National Comprehensive Cancer Network; NS: normal saline.

* 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 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. The Calvert formula is total dose (mg) = (target AUC) × (GFR + 25). If an estimated GFR based upon measured serum creatinine is used in the Calvert equation, and renal function is normal, clinicians should consider capping the GFR at 125 mL/min, at least for the first dose. This recommendation does not apply if the GFR is directly measured. Refer to UpToDate topics on dosing of anticancer agents in adults, section on carboplatin.

◊ Many clinicians use a slightly higher carboplatin dose (AUC 7.5 mg/mL × min) for patients with a good performance status.

§ Consensus-based guidelines from the NCCN classify higher carboplatin doses (AUC ≥4) as highly emetogenic; by contrast, the American Society of Clinical Oncology and the Multinational Association for Supportive Care in Cancer guidelines consider all carboplatin doses to be moderately emetogenic. Although many institutions classify carboplatin-containing regimens as moderately emetogenic, a benefit for adding a neurokinin 1 receptor antagonist on day 1 has been shown in many studies; additional prophylaxis beyond day 1 for delayed emesis is not needed for most patients. Refer to UpToDate topics on prevention and treatment of chemotherapy-induced nausea and vomiting in adults.

References:
  1. Bolis G, Scarfone G, Polverino G, et al. Paclitaxel 175 or 225 mg per meters squared with carboplatin in advanced ovarian cancer: a randomized trial. J Clin Oncol 2004; 22:686.
  2. Miller D, Filiaci V, Fleming G, et al. Late-Breaking Abstract 1: Randomized phase III noninferiority trial of first line chemotherapy for metastatic or recurrent endometrial carcinoma: A Gynecologic Oncology Group study. Gynecol Oncol 2012; 125:771.
  3. Tinker A, Bhagat K, Swenerton KD, Hoskins PJ. Carboplatin and paclitaxel for advanced and recurrent cervical carcinoma: the British Columbia Cancer Agency experience. Gynecol Oncol 2005; 98:54.
  4. Paclitaxel injection. United States Prescribing Information. US National Library of Medicine. (Available online at dailymed.nlm.nih.gov, accessed on October 29, 2019).
  5. 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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