Cycle length: Paclitaxel and trastuzumab weekly for 12 weeks; trastuzumab monotherapy every 3 weeks for 40 weeks (13 cycles).
Duration of therapy: One year or until disease progression or unacceptable toxicity. |
| Drug | Dose and route | Administration | Given on days |
| Trastuzumab* | Loading dose: 4 mg/kg IV¶ | Dilute in 250 mL NSΔ and administer over 90 minutes for the loading dose. Do not mix with D5W and do not infuse as an IV push or bolus. | Day 1 only |
| Trastuzumab* | 2 mg/kg IV¶◊ | Dilute in 250 mL NSΔ and administer over 30 minutes for subsequent doses. Do not mix with D5W and do not infuse as an IV push or bolus. | Day 8 then weekly for 11 weeks |
| Paclitaxel§ | 80 mg/m2 IV¶ | Dilute in 250 mL NSΔ and administer over one hour (final concentration range, 0.3 to 1.2 mg/mL); special tubing is needed.¥[2] Administer trastuzumab prior to paclitaxel when given concomitantly. | Day 1 then weekly for 12 weeks total (12 doses) |
| Trastuzumab* | 6 mg/kg IV¶ | Dilute in 250 mL NSΔ and administer over 30 minutes for subsequent doses. Do not mix with D5W and do not infuse as an IV push or bolus. | Every 3 weeks starting after week 12 for 13 doses |
| Pretreatment considerations: |
| Emesis risk | - LOW.
- Refer to UpToDate topics on prevention 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. Continue dexamethasone and H1 receptor antagonist for the first two doses; may drop in subsequent cycles if no hypersensitivity reactions. Most clinicians do not routinely premedicate prior to the first trastuzumab dose. However, patients may be instructed to self-administer acetaminophen or an NSAID if flu-like symptoms develop within 24 hours of trastuzumab administration.
- Refer to UpToDate topics on infusion reactions to systemic chemotherapy and infusion-related reactions to therapeutic monoclonal antibodies used for cancer therapy.
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| Cardiopulmonary issues | - Trastuzumab is associated with cardiotoxicity; assess baseline LVEF prior to therapy and then at least every 3 months during therapy. Patients with baseline LVEF <50% were excluded from this study.[1] Trastuzumab may cause serious pulmonary toxicity and should be used with caution in patients with preexisting pulmonary disease.[3]
- Refer to UpToDate topics on cardiotoxicity of trastuzumab and other HER2-targeted agents and pulmonary toxicity associated with antineoplastic therapy, molecularly targeted agents.
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| Vesicant/irritant properties | - Paclitaxel is an irritant but can cause significant tissue damage; avoid extravasation.
- Refer to UpToDate topics on extravasation injury from chemotherapy and other non-antineoplastic vesicants.
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| Infection prophylaxis | - Primary prophylaxis with G-CSF is not indicated; however, G-CSF was permitted during weekly paclitaxel for secondary prophylaxis.[1]
- Refer to UpToDate topics 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 | - 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 and chemotherapy hepatotoxicity and dose modification in patients with liver disease, molecularly targeted agents.
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| Monitoring parameters: |
- Obtain CBC with differential and platelet count prior to each administration of paclitaxel.
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- Assess electrolytes and liver and renal function prior to each administration of paclitaxel.
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- Monitor for infusion reactions, especially during the first two courses of trastuzumab.
- Refer to UpToDate topics on infusion-related reactions to therapeutic monoclonal antibodies used for cancer therapy.
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- Assess cardiac function at baseline and 3, 6, and 12 months after starting trastuzumab.[1]
- Refer to UpToDate topics on cardiotoxicity of trastuzumab and other HER2-targeted agents.
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- Assess changes in neurologic function prior to each dose of paclitaxel.
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| Suggested dose modifications for toxicity: |
| Myelotoxicity | - Weekly paclitaxel should only be administered if the ANC is >800/microL and platelets are ≥100,000/microL.[1] If the ANC is <800/microL or platelets are <100,000/microL, delay paclitaxel until count recovery and administer trastuzumab.
- No dosage adjustments for hematologic toxicity are recommended for this protocol except for febrile neutropenia.[1] For the second and subsequent episodes of febrile neutropenia, reduce remaining doses by 10 mg/m2.
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| Hepatotoxicity | - For grade 2 elevations in total bilirubin, transaminases, and/or ALP during therapy, hold paclitaxel for one week, and if the abnormal tests improve to grade 1 or 0, continue paclitaxel at full dose.[1] If the elevations remain at grade 2, continue paclitaxel at 70 mg/m2, and if they subsequently return to grade 0 or 1, return to full dose, 80 mg/m2. Patients should permanently discontinue treatment if grade 3 or 4 toxicity occurs.[1]
- 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.
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| Neurotoxicity | - No paclitaxel dose modifications are required for grade 1 or 2 neurotoxicity.[1] For grade 3 neurotoxicity, delay paclitaxel until toxicity has resolved to ≤grade 2, and reduce subsequent doses by 10 mg/m2 if resolution to ≤grade 2 within 2 weeks. If resolution requires >2 weeks or grade 4 neurotoxicity is reached, patient should discontinue treatment. If grade 3 neurotoxicity develops with additional infusions, further dose reductions may be made in increments of 10 mg/m2.
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| Cardiotoxicity | - Guidelines for managing trastuzumab in patients with symptomatic or asymptomatic cardiac dysfunction during therapy are available.[1]
- Refer to UpToDate topics on cardiotoxicity of trastuzumab and other HER2-targeted agents.
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| Pulmonary toxicity | - Discontinue trastuzumab for serious pulmonary toxicity.
- Refer to UpToDate topics on pulmonary toxicity associated with antineoplastic therapy: Molecularly targeted agents.
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| Infusion reactions | - Respond as clinically indicated with supportive care and possible discontinuation of therapy for severe reactions.
- Refer to UpToDate topics on infusion-related reactions to therapeutic monoclonal antibodies used for cancer therapy.
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| Other grade 3 or 4 toxicity | - For most other grade 3 or 4 toxicities (diarrhea, mucositis), delay treatment until toxicity resolves to grade 1 or 0, then resume treatment with a reduced dose of paclitaxel. Recommendations for paclitaxel dose reduction or discontinuation are available.[1]
- Trastuzumab: No dose modifications are permitted. If paclitaxel is delayed for any reason other than cardiotoxicity or severe hypersensitivity reactions that occurred when both paclitaxel and trastuzumab were administered, trastuzumab may be continued.
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| If there is a change in body weight of at least 10%, doses should be recalculated. |
