| Cycle length: 4 weeks. |
| Drug | Dose and route | Administration | Given on days |
| Nabpaclitaxel* | 125 mg/m2 IV | Administer undiluted over 30 minutes. | Days 1, 8, and 15¶ |
| Gemcitabine | 1000 mg/m2 IV | Dilute in 250 mL NSΔ (concentration no greater than 40 mg/mL) and administer over 30 to 60 minutes, after nabpaclitaxel. | Days 1, 8, and 15¶ |
| Pretreatment considerations: |
| Emesis risk | - MODERATE.
- Refer to UpToDate topics on prevention of chemotherapy-induced nausea and vomiting in adults.
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| Vesicant/irritant properties | - Nabpaclitaxel 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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| Prophylaxis for infusion reactions | - Premedication to prevent hypersensitivity reactions is generally not needed. Premedication may be needed in patients who have had a prior hypersensitivity reaction to nabpaclitaxel.
- Refer to UpToDate topics on infusion reactions to systemic chemotherapy.
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| Infection prophylaxis | - The incidence of febrile neutropenia with this regimen is 3%.[1] Primary prophylaxis with G-CSF is not indicated.
- 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 for gemcitabine and nabpaclitaxel may be needed for patients with liver impairment. Do not administer nabpaclitaxel to patients with pancreatic cancer and moderate to severe liver impairment (AST <10 times the ULN and total bilirubin >1.5 times the ULN OR AST >10 times the ULN OR bilirubin >5 times the ULN).
- 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: |
- CBC with differential and platelets weekly during treatment.
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- Assess comprehensive metabolic panel prior to each cycle or when clinically indicated during treatment.
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- Monitor for infusion reactions.
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- Monitor for extravasation.
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- Sensory neuropathy occurs frequently with nabpaclitaxel; assess for changes in neurologic function prior to each treatment cycle.
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- Monitor for signs and symptoms of pneumonitis.
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| Suggested dose modifications for toxicity: |
| Myelotoxicity | - Do not administer nabpaclitaxel and gemcitabine on day 1 of each new cycle unless ANC is >1500/microL and platelet count is >100,000/microL.[2,3] For patients who develop neutropenic fever OR ANC <500/microL for >7 days or delay of next cycle by >7 days or thrombocytopenia, withhold treatment until counts recover to an ANC of at least 1500/microL and platelet count of at least 100,000/microL on day 1, or to an ANC of at least 500/microL and platelet count of at least 50,000/microL on days 8 or 15 of the cycle.[2,3] Upon resumption of therapy, reduce both drugs by 20 to 25% upon the first occurrence, an additional 20 to 25% on the second recurrence, and discontinue treatment for a third occurrence.
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| Sepsis | - Sepsis has occurred in patients with or without neutropenia (risk factors are biliary obstruction or presence of a biliary stent). Initiate broad-spectrum antibiotics in the presence of fever, even if not neutropenic. Interrupt nabpaclitaxel and gemcitabine until sepsis resolves and, if neutropenic, until neutrophils are at least 1500/microL, then resume at lower doses.[3]
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| Thrombotic microangiopathy | - Thrombotic microangiopathy (TMA; also sometimes called thrombotic thrombocytopenic purpura [TTP] or hemolytic uremic syndrome [HUS]) has been associated with gemcitabine in individuals who have received a large or small cumulative dose.[4] Consider the possibility of TMA if the patient develops Coombs-negative hemolysis, thrombocytopenia, renal failure, and/or neurologic findings. Management consists of drug discontinuation and supportive care, without plasma exchange, as long as there is high confidence in a drug-induced etiology rather than TTP.
- Refer to UpToDate topics on drug-induced thrombotic microangiopathy.
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| Peripheral neuropathy | - For days 1,8, and 15: withhold nabpaclitaxel for grade 3 or 4 neuropathy.[2,3] Resume nabpaclitaxel at 20 to 25 percent reduced doses when peripheral neuropathy improves to grade ≤2 or completely resolves. Upon resumption of therapy, reduce nabpaclitaxel by 20 to 25% for the first occurrence of grade 3 or 4 peripheral neuropathy, and an additional 20 to 25% for the second occurrence.[3] Discontinue treatment for a third occurrence.[3] For grade 2 peripheral neuropathy, decrease nabpaclitaxel dose by 20 to 25%.[2]
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| Hepatotoxicity | - Gemcitabine is commonly associated with a transient rise in serum transaminases, but these are seldom of clinical significance. There is insufficient information from clinical studies to allow clear gemcitabine dose recommendations in these patients.
- Reduced starting doses of nabpaclitaxel are recommended for individuals with pre-existing moderate to severe hepatic impairment; the need for further dose adjustments in subsequent courses based upon ongoing hepatotoxicity should be based on individual tolerance and clinician judgment.[3]
- One protocol recommends the following:[2] on days 1, 8, and 15, for serum bilirubin elevations ≥grade 2, withhold both drugs until toxicity resolves to grade ≤1; resume treatment at the same dose as before. If not resolved, discontinue therapy.
- 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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| Pulmonary toxicity | - A variety of manifestations of pulmonary toxicity have been reported with gemcitabine. Pneumonitis has occurred with the use of nabpaclitaxel in combination with gemcitabine. Permanently discontinue treatment with both agents.[3]
- Refer to UpToDate topics on pulmonary toxicity associated with antineoplastic therapy, cytotoxic agents.
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| Other toxicity | - On days 1, 8, and 15: for grade 3 cutaneous toxicity, hold both drugs until recovered to ≤grade 2, and reduce nabpaclitaxel dose by 20 to 25% and gemcitabine dose by 20%.[2] For grade 3 mucositis or diarrhea, withhold therapy until it improves to ≤grade 1, then resume with reduction of nabpaclitaxel dose by 20 to 25% and gemcitabine dose by 20%.
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| If there is a change in body weight of at least 10%, doses should be recalculated. |
