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Carboplatin plus docetaxel for advanced non-small cell lung cancer[1]

Carboplatin plus docetaxel for advanced non-small cell lung cancer[1]
Cycle length: Every 21 days, for a maximum of six cycles.
Drug Dose and route Administration Given on days
Carboplatin AUC* = 6 mg/mL × min IV Dilute in 250 mL NS and administer over 30 minutes. Carboplatin should be administered after the completion of docetaxel infusion. Day 1
Docetaxel 75 mg/m2 IV Dilute in 250 mL NS to a final concentration of 0.3 to 0.74 mg/mL and administer over 60 minutes. Docetaxel should be infused prior to carboplatin. Day 1
Pretreatment considerations:
Emesis risk
  • MODERATE.Δ
  • Refer to UpToDate topic on "Prevention and treatment of chemotherapy-induced nausea and vomiting in adults".
Prophylaxis for infusion reactions
  • Premedicate with dexamethasone prior to docetaxel administration.[2]
  • Refer to UpToDate topic on "Infusion reactions to systemic chemotherapy".
Vesicant/irritant properties
  • Carboplatin and docetaxel are irritants, but 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 hematopoietic growth factors is not recommended (incidence of febrile neutropenia approximately 4%[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
  • Each carboplatin dose should be calculated based upon renal function by use of the Calvert formula.* Docetaxel should not be administered to patients with a serum bilirubin above the ULN or to patients with transaminase elevations >1.5 × ULN in conjunction with alkaline phosphatase >2.5 × ULN.
  • Refer to UpToDate topics on "Dosing of anticancer agents in adults" and "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".
Dose adjustment for known drug interactions
  • Caution is required if administering docetaxel with strong CYP3A4 inhibitors.◊ According to the United States Prescribing Information, avoid the use of docetaxel with strong CYP3A4 inhibitors (if possible). If concomitant therapy cannot be avoided, monitor closely for toxicity and consider a docetaxel dose reduction.[2] Docetaxel dose reductions for concomitant therapies should be individualized based on patient factors (eg, performance status) and the intent of therapy (ie, curative or palliative).
  • Refer to "Suggested dose modifications for toxicity" below.
Monitoring parameters:
  • CBC with differential and platelet count prior to each cycle of treatment.
  • Electrolytes and liver and renal function prior to each cycle of treatment.
  • Patients with renal impairment, hyperuricemia, and bulky tumors are at risk for TLS and should undergo correction of dehydration and lowering of high serum uric acid levels prior to treatment initiation, and be closely monitored for TLS during and after treatment.
  • Refer to UpToDate topics on "Tumor lysis syndrome: Definition, pathogenesis, clinical manifestations, etiology and risk factors" and "Tumor lysis syndrome: Prevention and treatment".
Suggested dose modifications for toxicity:
Myelotoxicity
  • The United States Prescribing Information recommends reducing the dose of carboplatin by 25% if platelets are <50,000/microL and/or ANC is <500/microL.[3] Docetaxel should only be administered if the ANC is >1500/microL. A 25% dose reduction of docetaxel is recommended for subsequent cycles in patients who develop severe prolonged neutropenia (<500/microL lasting seven days or more), febrile neutropenia, or a grade 4 infection (ie, an infection with life-threatening consequences).[2]
Nonhematologic toxicity
  • No formal dosing recommendations were reported in the final publication.[1] However, dose reductions for each agent may be needed for serious nonhematologic toxicity.
  • Refer to UpToDate topics on "Carboplatin: Drug information" and "Docetaxel: Drug information".
Cutaneous, mucosal, and neurologic toxicity
  • For severe or cumulative cutaneous reactions (erythema and desquamation), grade 3 or 4 stomatitis, or moderate neurosensory signs and/or symptoms, the dose of docetaxel should be reduced from 75 to 60 mg/m2.[2] If toxicity persists, treatment should be discontinued.
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.

AUC: area under the concentration × time curve; IV: intravenous; NS: normal saline; ULN: upper limit of normal; CYP3A4: cytochrome P450 3A4; CBC: complete blood count; TLS: tumor lysis syndrome; ANC: absolute neutrophil count; GFR: glomerular filtration rate; NCCN: National Comprehensive Cancer Network.

* 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 using measured serum creatinine, limit the maximal GFR for the calculation to 125 mL/min. Refer to UpToDate topic on "Dosing of anticancer agents in adults".

¶ Diluent solutions should not be modified without consulting a detailed reference due to potential incompatibility(ies).

Δ 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 topic on "Prevention and treatment of chemotherapy-induced nausea and vomiting in adults".

◊ A list of strong and moderate CYP3A4 inhibitors is available as a separate table in UpToDate. Specific interactions may be determined by use of the Lexicomp drug interactions program included within UpToDate.
References:
  1. Fossella F, et al. J Clin Oncol 2003; 21:3016.
  2. Docetaxel injection. United States Prescribing Information. US National Library of Medicine. (Available online at dailymed.nlm.nih.gov, accessed on March 15, 2022).
  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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