Cycle length: 28 days.
Duration of therapy: Until disease progression or unacceptable toxicity. |
| Drug | Dose and route | Administration | Given on days |
| Paclitaxel | 80 mg/m2 IV | Mix in 250 mL NS or D5W* and administer over 1 hour.¶ | Days 1, 8, and 15 |
| Carboplatin | AUCΔ = 5 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 on day 1;
LOW on days 8 and 15.◊ - Refer to UpToDate topics on prevention of chemotherapy-induced nausea and vomiting in adults.
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| Prophylaxis for infusion reactions | - Premedicate with a glucocorticoid and H1 and H2 receptor blockers prior to paclitaxel administration. Patients who receive paclitaxel on a weekly basis have the potential to receive substantial doses of dexamethasone; ongoing glucocorticoid treatment is unnecessary in most. One approach to minimizing glucocorticoid use is to administer a lower dexamethasone dose (10 mg IV) with an H1 and H2 receptor blocker 30 minutes prior to the first administration of weekly paclitaxel. Glucocorticoid doses can then be safely tapered by weekly 2-mg decrements in patients without infusion reactions, and eventually discontinued.[2,3]
- Carboplatin is also associated with infusion reactions. However, they usually occur after at least six cycles, and no specific premedication regimen is recommended.
- Refer to UpToDate topics on infusion reactions to systemic chemotherapy.
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| 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".
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| Infection prophylaxis | - Primary prophylaxis with G-CSF not recommended. The trial reported a 5% rate of febrile neutropenia and 29% grade 3 or 4 neutropenia.[1]
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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[4] A lower starting dose of paclitaxel may be needed in patients with liver impairment.[5]
- Refer to UpToDate topics on chemotherapy hepatotoxicity and dose modification in patients with liver disease, conventional cytotoxic agents and dosing of anticancer agents in adults.
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| Monitoring parameters: |
- CBC with differential on each treatment day.
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- Serum electrolytes and liver and renal function tests prior to each new treatment cycle.
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- Assess changes in neurologic function prior to each new treatment cycle.
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- Monitor for infusion reactions and extravasation.
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| Suggested dose modifications for toxicity[1]: |
| Myelotoxicity | - For a new cycle of therapy, delay treatment until the ANC is ≥1500/microL and the platelet count is ≥100,000/microL.[1] If hematologic recovery requires >7 days and the day 29 ANC is <1000/microL, reduce day 1 carboplatin by 1 AUCΔ unit (ie, from 5 to 4 mg/mL per min). If hematologic recovery requires >7 days and the day 1 platelet count is <50,000/microL, reduce day 1 paclitaxel from 80 to 70 mg/m2. For the second occurrence, reduce carboplatin by an additional AUCΔ unit, and reduce paclitaxel to 60 mg/m2.
- Omit the day 8 and 15 doses of paclitaxel if any of the following occurs within 24 hours prior to administration: ANC <1000/microL, platelets <75,000/microL, or hemoglobin ≤8 g/dL. Omitted doses are not made up. If the ANC was <1000/microL or the platelet count was <75,000/microL on day 8 or 15, reduce carboplatin dose for the next cycle by 1 AUCΔ unit. If the platelet count was <50,000/microL on day 8 or 15, reduce paclitaxel dose for the next cycle from 80 mg/m2 to 70 mg/m2. For the second occurrence, reduce paclitaxel to 60 mg/m2.
- If day 15 paclitaxel administration has been omitted due to hematologic toxicity and the criteria for treatment continuation on day 1 of the next cycle are not met, reduce day 1 carboplatin by 1 AUCΔ unit, and reduce day 1 paclitaxel by 1 dose level.
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| Neurologic toxicity | - For grade 2 or worse sensory or motor peripheral neuropathy, interrupt therapy until resolved to ≤grade 1; on recovery, reduce paclitaxel dose from 80 to 70 mg/m2 for subsequent courses.[1] For delay in recovery >2 weeks, or any grade 3 or worse neuropathy, discontinue paclitaxel.
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| Liver or renal dysfunction | - Alterations in renal function during therapy may require a recalculation of the carboplatin dose.[4] The development of grade 2 or worse elevations in AST, ALT, ALP, or bilirubin requires reduction in paclitaxel dose from 80 to 70 mg/m2 after recovery to ≤grade 1.[1]
- 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.
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| Other toxicity | - For grade 3 or worse diarrhea on the day of treatment, hold paclitaxel. Once resolved to ≤grade 1, reduce dose from 80 to 70 mg/m2 for future cycles.[1]
- For grade ≥3 mucositis, delay treatment until resolved to ≤grade 1, and reduce paclitaxel from 80 to 70 mg/m2.[1] For second occurrence, or if grade 3 or worse mucositis persists for more than 2 weeks, discontinue paclitaxel.
- For all other nonhematologic toxicities grade 3 or worse (except alopecia, constipation, nausea, and infusion reactions), hold therapy until resolved to ≤grade 1.
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| If there is a change in body weight of at least 10%, doses should be recalculated. |
