Cycle length: Every 21 days for a maximum of six cycles, followed by maintenance therapy with bevacizumab every three weeks. |
Drug | Dose and route | Administration | Given on days |
Paclitaxel | 200 mg/m2 IV | Dilute in 250 mL NS* (final concentration of 0.3 to 1.2 mg/mL) and administer over three hours.¶ | Day 1 |
Carboplatin | AUCΔ = 6 mg/mL per min IV | Dilute in 250 mL NS* and administer over 30 minutes (administer 60 minutes after the completion of the paclitaxel infusion). | Day 1 |
Bevacizumab | 15 mg/kg IV | Dilute into a total volume of 100 mL of NS.* The first dose should be administered over 90 minutes one hour after carboplatin. If well tolerated, the second infusion may be administered over 60 minutes. If well tolerated, all subsequent infusions may be administered over 10 to 30 minutes.[2] | Day 1 |
Pretreatment considerations: |
Emesis risk | - MODERATE (MINIMAL when bevacizumab is given as maintenance).◊
- Refer to UpToDate topic on "Prevention and treatment of chemotherapy-induced nausea and vomiting in adults".
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Prophylaxis for infusion reactions | - Premedicate with dexamethasone plus both an H1 and an H2 receptor antagonist prior to paclitaxel administration. There is no standard premedication regimen for bevacizumab.
- Refer to UpToDate topic on "Infusion reactions to systemic chemotherapy".
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Vesicant/irritant properties | - Paclitaxel can cause significant tissue damage and carboplatin is an irritant; avoid extravasation.
- Refer to UpToDate topic on "Extravasation injury from chemotherapy and other non-antineoplastic vesicants".
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Infection prophylaxis | - Primary prophylaxis with hematopoietic growth factors is not recommended (risk of febrile neutropenia is approximately 5%[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".
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Dose adjustment for baseline liver or renal dysfunction | - Each carboplatin dose should be calculated based upon renal function by use of the Calvert formula.Δ
- A lower starting dose of paclitaxel may be needed in patients with liver impairment. Bevacizumab does not require dosage adjustments for liver or renal dysfunction.[2]
- 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".
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Monitoring parameters: |
- CBC with differential weekly during treatment.
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- Serum electrolytes and liver and renal function tests prior to each treatment cycle.
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- Assess changes in neurologic function, blood pressure, urine protein concentration, and risk for bleeding prior to each treatment cycle.
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Suggested dose modifications for toxicity: |
Myelotoxicity | - Treatment with paclitaxel and carboplatin should be delayed until the ANC is >2000/microL and platelet count is >100,000/microL.[3,4] If a patient develops 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.[5] An alternative to dose reduction is the institution of hematopoietic growth factor support. Both the carboplatin and paclitaxel doses should be decreased by 25% in patients whose platelet count nadir is <50,000/microL for longer than five days.[4]
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Renal/hepatic toxicity | - Alterations in renal 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" and "Dosing of anticancer agents in adults".
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Neurotoxicity | - For patients who develop severe peripheral neuropathy (grade 3 or 4) for a week or longer, the dose of paclitaxel should be reduced by 20% for subsequent courses.[4]
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Other toxicity | - Assess changes in blood pressure, urine protein concentration, and risk for bleeding prior to each treatment. Discontinue bevacizumab for hypertensive crisis or hypertensive encephalopathy, serious hemorrhage, arterial thromboembolism, nephrotic syndrome, gastrointestinal perforation, fistula formation, or RPLS.[2] Do not administer within 28 days of surgery.
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If there is a change in body weight of at least 10%, doses should be recalculated. |
Dose reductions may also be indicated if there are other grade 2 or higher nonhematologic toxicities. The dose reduction is at the discretion of the clinician, as formal guidelines are not available. |