Cycle length: 21 days.
Duration of therapy: Until disease progression or for 2 cycles beyond best response. 4 cycles minimum is recommended for stable disease. |
| Drug | Dose and route | Administration | Given on days |
| Topotecan | 2.3 mg/m2 per day by mouth*¶ | By mouth: Administer once daily without regard to meals. Do not open or crush capsule. | Daily, days 1 though 5 |
| OR | |
| 1.5 mg/m2 once per day IV* | IV: Dilute in 100 mL NS or D5WΔ and administer over 30 minutes. |
| Pretreatment considerations: |
| Emesis risk | - LOW.
- Refer to UpToDate topics on prevention of chemotherapy-induced nausea and vomiting in adults.
|
| Prophylaxis for infusion reactions | - Routine prophylaxis not indicated.
- Refer to UpToDate topics on infusion reactions to systemic chemotherapy.
|
| Vesicant/irritant properties | - Topotecan is an irritant; however, rare severe cases of extravasation have been reported.[2]
- 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 is 5%◊[1]). In the event of severe neutropenia (ANC <500/microL), hematopoietic growth factors may be considered beginning on day 6 for subsequent cycles of IV topotecan.[2]
- 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 renal dysfunction | - Dose adjustments for topotecan in patients with renal impairment are recommended.
- Refer to UpToDate topics on chemotherapy nephrotoxicity and dose modification in patients with renal insufficiency, conventional cytotoxic agents.
|
| Monitoring parameters: |
- CBC with differential and platelet count weekly during treatment.
|
- Basic metabolic panel and liver function tests prior to each cycle.
|
| Suggested dose modifications for toxicity: |
| Myelotoxicity | - Prior to administration of the first course of treatment, patients should have a platelet count of >100,000/mm3 and an ANC >1000/microL.[2,3] For IV topotecan: If the ANC falls below 500/microL or platelets fall below 25,000/microL at any time during the cycle, consider dose-reducing IV topotecan by 0.25 mg/m2 per day, for subsequent cycles. An alternative for patients who develop severe neutropenia is administering granulocyte-colony stimulating factors for subsequent courses (starting on day 6 of the subsequent cycle) before resorting to dose reduction.[2] IV topotecan-associated neutropenia may predispose to neutropenic colitis. In patients presenting with fever, neutropenia, and a compatible picture of abdominal pain with or without diarrhea, neutropenic colitis should be suspected.
- Refer to UpToDate topics on neutropenic enterocolitis (typhlitis).
|
| Pulmonary toxicity | - IV topotecan has been associated with fatal reports of interstitial lung disease. Monitor patients for pulmonary symptoms indicative of interstitial lung disease and discontinue topotecan if a new diagnosis of interstitial lung disease is confirmed.[2,3]
- Refer to UpToDate topics on pulmonary toxicity associated with antineoplastic therapy, cytotoxic agents.
|
| Diarrhea | - Hold oral topotecan for grade 3 or 4 diarrhea. When resolved to ≤grade 1, reduce dose by 0.4 mg/m2 per day for subsequent cycles.[3]
|
| If there is a change in body weight of at least 10%, doses should be recalculated. |
