| Cycle length: 21 days, for a maximum of six cycles. |
| Drug | Dose and route | Administration | Given on days |
| Pemetrexed | 500 mg/m2 IV | Dilute in 100 mL NS* and administer over 10 minutes. Do not administer with calcium-containing IV fluids such as lactated Ringer solution. | Day 1 |
| Cisplatin | 75 mg/m2 IV | Dilute in 250 mL NS* and administer over 120 minutes, beginning 30 minutes after pemetrexed. Do not administer with aluminum needles or sets. | Day 1 |
| Pretreatment considerations: |
| Hydration | - IV fluid to establish a urine flow of at least 100 mL/hour for at least two hours prior to and two hours after cisplatin administration.
- Refer to UpToDate topics on cisplatin nephrotoxicity.
|
| Emesis risk | - HIGH.
- Refer to UpToDate topics on prevention of chemotherapy-induced nausea and vomiting in adults.
|
| Prophylaxis for skin rashes | - Premedication with dexamethasone (4 mg orally twice daily for three days starting the day before drug administration) is recommended to reduce cutaneous toxicity.[3]
- Refer to UpToDate topics on cutaneous complications of conventional chemotherapy agents.
|
| Vesicant/irritant properties | - Cisplatin 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.
|
| Infection prophylaxis | - Primary prophylaxis with hematopoietic growth factors is not recommended (incidence of neutropenic fever approximately 2%[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.
|
| Dose adjustment for baseline liver or kidney dysfunction | - The optimal approach to cisplatin therapy in patients with preexisting kidney impairment is unknown. Such patients were excluded from the original trial.[1] With pemetrexed, avoid use if CrCl is <45 mL/min. There are recommendations for avoidance of NSAIDs in the days prior to and immediately following each dose of pemetrexed in patients with mild to moderate kidney dysfunction (CrCl 45 to 79 mL/min) because of the potential for decreased clearance of pemetrexed.
- Refer to UpToDate topics on 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; chemotherapy nephrotoxicity and dose modification in patients with kidney impairment, conventional cytotoxic agents; and pemetrexed: drug information.
|
| Vitamin supplementation | - Vitamin supplementation with folic acid and intramuscular B12 is recommended prior to administration of pemetrexed and during treatment to reduce both hematologic and nonhematologic side effects.[1,3]
|
| Monitoring parameters: |
- CBC with differential and platelet count weekly during treatment.
|
- Electrolytes, kidney, and liver function weekly during treatment.
|
- Monitor for hearing loss prior to each dose of cisplatin; audiometry as clinically indicated.
|
| Suggested dose modifications for toxicity: |
| Myelotoxicity | - Each cycle should not begin until the ANC count is >1500/microL and platelet count is >100,000/microL.[1] During treatment, if nadir ANC is <500/microL and nadir platelet count is ≥50,000/microL, reduce dose of both pemetrexed and cisplatin by 25%. Regardless of the ANC, reduce dose of both pemetrexed and cisplatin by 25% if nadir platelet count is <50,000/microL without bleeding. If nadir platelet count is <50,000/microL with bleeding, reduce dose of both pemetrexed and cisplatin by 50%.[1,3]
- 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.
|
| Neurologic toxicity | - Neuropathy usually is seen only after cumulative doses of cisplatin beyond 400 mg/m2, although there is marked interindividual variation.
- Refer to UpToDate topics on overview of neurologic complications of platinum-based chemotherapy.
|
| Nephrotoxicity | - Hold cisplatin until serum creatinine is <1.5 mg/dL and/or blood urea nitrogen is <25 mg/dL. For grade ≥2 nephrotoxicity during treatment (creatinine >1.5 times normal value despite adequate hydration), CrCl should be determined prior to next cycle and cisplatin dose reduced if <60 mL/min. Treatment with pemetrexed should not begin unless CrCl is ≥45 mL/min.
|
| Mucositis, hepatotoxicity, and other severe non-hematologic toxicity | - The dose of pemetrexed should be reduced 50% for grade 3 or 4 mucositis. The doses of pemetrexed and cisplatin should be decreased to 75% of previous level for any other grade 3 or 4 toxicities or for any diarrhea requiring hospitalization.
|
| If there is a change in body weight of at least 10%, doses should be recalculated. |
