| Cycle length: 21 days. |
| Drug | Dose and route | Administration | Given on days |
| Gemcitabine | 900 mg/m2 IV (for soft tissue sarcoma if no prior pelvic radiation therapy [RT]*) | Dilute with 250 mL normal saline (NS) (final concentration <40 mg/mL) and administer over 90 minutes (ie, 10 mg/m2 per min). | Days 1 and 8 |
| Docetaxel | 75 or 100 mg/m2 IV (if no prior pelvic RT)¶ | Dilute with 250 mL NS (final concentration of 0.3 to 0.74 mg/mL) and administer over 60 minutes. | Day 8 |
| Pretreatment considerations: |
| Emesis risk | - MODERATE (30 to 90% frequency of emesis).
- 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 prior to docetaxel administration.[2]
- Refer to UpToDate topics on infusion reactions to systemic chemotherapy.
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| Vesicant/irritant properties | - Docetaxel 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 | - This regimen was designed to include primary prophylaxis with granulocyte colony stimulating factors (starting on day 9).[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 kidney dysfunction | - Docetaxel should not be administered if serum bilirubin is above the ULN or if the AST and/or ALT are >1.5 times ULN concomitant with alkaline phosphatase >2.5 times ULN.[2] A lower starting dose of gemcitabine may be needed in patients with impaired liver function.
- 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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| Dose adjustment for known drug interactions | - Caution is required if administering docetaxel with strong CYP3A4 inhibitors.Δ According to the United States Prescribing Information, avoid the use of docetaxel with strong CYP3A4 inhibitors (if possible). If concomitant therapy cannot be avoided, monitor closely for toxicity and consider a docetaxel dose reduction.[2] Docetaxel dose reductions for concomitant therapies should be individualized based on patient factors (eg, performance status) and the intent of therapy (ie, curative or palliative).
- Refer to "Suggested dose modifications for toxicity" below.
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| Monitoring parameters: |
- Monitor CBC with differential and platelet count weekly during treatment.
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- Assess basic metabolic panel (including serum creatinine) and liver function tests prior to each treatment cycle.
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- Assess for neuropathy, pulmonary toxicity, and fluid retention (weight gain, shortness of breath, peripheral edema, ascites) during treatment.
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- Patients with kidney impairment, hyperuricemia, and bulky tumors are at risk for TLS and should undergo correction of dehydration and lowering of high serum uric acid levels prior to treatment initiation, and be closely monitored for TLS during and after treatment.
- Refer to UpToDate topics on tumor lysis syndrome.
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| Suggested dose modifications for toxicity: |
| Myelotoxicity | - The original protocol used the following dose adjustment parameters.[1] For febrile neutropenia or a platelet count <25,000/microL lasting more than five days, reduce dose of both gemcitabine and docetaxel by 25% for all subsequent cycles. Delay treatment by one week if the day 1 ANC is <1000 cells/microL or platelet count <100,000/microL; discontinue treatment if not recovered to these levels after two weeks. If day 8 ANC is 500 to 999 cells/microL or platelet count 50,000 to 99,000/microL, reduce gemcitabine and docetaxel by 25%. If ANC <500 cells/microL or platelets <50,000/microL on day 8, eliminate day 8 doses of both drugs for that cycle.
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| Neurotoxicity | - For grade 3 or 4 neurotoxicity, delay treatment one week; if neurotoxicity resolves to ≤grade 2, resume treatment with docetaxel dose reduced by 25% of the previous dose for all subsequent cycles.
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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, kidney 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 in patients treated with gemcitabine. Discontinue treatment immediately and permanently.
- Refer to UpToDate topics on pulmonary toxicity associated with antineoplastic therapy, cytotoxic agents.
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| Hepatotoxicity | - For bilirubin level >1.5 mg/dL, hold docetaxel for that cycle. If bilirubin returns to <1.5 mg/dL, resume docetaxel treatment in subsequent cycles.[1] 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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| Other toxicities | - For all other grade 3 or 4 nonhemalogic toxicities (except alopecia), hold treatment for up to two weeks; resume treatment when toxicity has resolved to <grade 2.
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| If there is a change in body weight of at least 10%, doses should be recalculated. |
