Cycle length: 21 days.
Maximum: Six cycles. |
| Drug | Dose and route | Administration | Given on days |
| Oxaliplatin | 80 mg/m2 IV* | Dilute in 500 mL D5W¶ and administer over two hours. Shorter oxaliplatin administration schedules (eg, 1 mg/m2 per minute) appear to be safe.[2] | Days 1 and 8 |
| Gemcitabine | 900 mg/m2 IV | Dilute in 250 mL NS¶ (concentration no more than 40 mg/mL) and administer over 30 minutes. | Days 1 and 8 |
| Pretreatment considerations: |
| Emesis risk | - MODERATE on days 1 and 8.
- Refer to UpToDate topics on prevention of chemotherapy-induced nausea and vomiting in adults.
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| Vesicant/irritant properties | - Oxaliplatin 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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| Prophylaxis for infusion reactions | - Routine prophylaxis is not indicated for gemcitabine or oxaliplatin.
- Refer to UpToDate topics on infusion reactions to systemic chemotherapy.
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| Infection prophylaxis | - 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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| Maneuvers to prevent neurotoxicity | - Pharmacologic methods to prevent/delay the onset of oxaliplatin-related neuropathy are controversial due to the absence of large clinical trials proving benefit. Counsel patients to avoid exposure to cold during and for approximately 48 hours after each infusion. Prolongation of the oxaliplatin infusion time from two to six hours may mitigate acute neurotoxicity.
- Refer to UpToDate topics on overview of neurologic complications of platinum-based chemotherapy.
|
| Dose adjustment for baseline liver or renal dysfunction | - A lower starting dose of gemcitabine may be needed for patients with liver impairment.[3] A lower starting dose of oxaliplatin may be needed for severe renal impairment.[4]
- Refer to UpToDate topics on chemotherapy nephrotoxicity and dose modification in patients with renal insufficiency, conventional cytotoxic agents; chemotherapy hepatotoxicity and dose modification in patients with liver disease, conventional cytotoxic agents; chemotherapy hepatotoxicity and dose modification in patients with liver disease, molecularly targeted agents.
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| Cardiac issues | - QT prolongation and ventricular arrhythmias have been reported after oxaliplatin. ECG monitoring is recommended if therapy is initiated in patients with heart failure, bradyarrhythmias, coadministration of drugs known to prolong the QT interval, and electrolyte abnormalities. Avoid oxaliplatin in patients with congenital long QT syndrome. Correct hypokalemia and hypomagnesemia prior to initiating oxaliplatin.
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| Monitoring parameters: |
- Assess electrolytes (especially potassium and magnesium) and liver and renal function prior to each treatment.
|
- Assess CBC with differential prior to each treatment.
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- Assess pulmonary function prior to each new treatment cycle.
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- Monitor for neurotoxicity prior to each new treatment cycle.
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| Suggested dose modifications for toxicity: |
| Myelotoxicity | - A new cycle of treatment should not start until the ANC is ≥1500/microL and platelet count is ≥100,000/microL. Intracycle dose reduction for day 8 treatment: If ANC is <1000/microL and/or platelets are <50,000/microL, interrupt treatment until recovery to ANC ≥1500/microL and platelet count is ≥75,000/microL. In the event of grade IV neutropenia or thrombocytopenia, reduce chemotherapy doses by 25% once counts have recovered.[5]
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| Neurotoxicity | - For >grade 1 peripheral sensory neuropathy persisting over seven days, reduce dose of oxaliplatin by 25%. Discontinue oxaliplatin for grade 3 or 4 peripheral sensory neuropathy.[5]
|
| 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 dose recommendations in these patients.
- 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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| 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.[3] 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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| Pulmonary toxicity | - A variety of manifestations of pulmonary toxicity have been reported with gemcitabine. Discontinue gemcitabine immediately and permanently. Oxaliplatin has rarely been associated with pulmonary toxicity. Withhold oxaliplatin for unexplained pulmonary symptoms until interstitial lung disease or pulmonary fibrosis is excluded.
- Refer to UpToDate topics on pulmonary toxicity associated with antineoplastic therapy, molecularly targeted agents and pulmonary toxicity associated with antineoplastic therapy, cytotoxic agents.
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| If there is a change in body weight of at least 10%, doses should be recalculated. |
