Vaginal Cancer Regimen: Topotecan + Cisplatin (Topocis)

by Hematology-Oncology Therapy

Update to Chapter 38: Vaginal Cancer

Zanaboni F et al. Eur J Cancer 2013;49:1065–1072

The regimen consists of 2 cycles of neoadjuvant chemotherapy followed by radical surgery in patients without disease progression. Postoperative adjuvant radiation therapy, with or without chemotherapy, may be administered in patients with poor prognostic factors such as cut-through surgical margins, positive lymph nodes, parametrial involvement, or vaginal involvement

Topotecan HCl 2 mg/m² per dose; administer intravenously in 50–250 mL 0.9% sodium chloride injection (0.9% NS) or 5% dextrose injection over 30 minutes once weekly for 3 doses on days 1, 8, and 15, every 28 days for 2 cycles (total dosage/cycle = 6 mg/m²), followed by:

Hydration before cisplatin: ≥1000 mL 0.9% NS; administer intravenously over a minimum of 2–4 hours

Cisplatin 40 mg/m² per dose; administer intravenously in 50–500 mL 0.9% NS over 60 minutes once weekly for 3 doses on day 1, 8, and 15, every 28 days for 2 cycles (total dosage/cycle = 120 mg/m²)

Hydration after cisplatin: ≥1000 mL 0.9% NS; administer intravenously over a minimum of 2–4 hours. Encourage patients to increase oral intake of nonalcoholic fluids. Monitor serum electrolytes and replace as needed (potassium, magnesium, sodium)

Supportive Care

Antiemetic prophylaxis

Emetogenic potential is HIGH. Potential for delayed symptoms

See Chapter 39 for antiemetic recommendations

Hematopoietic growth factor (CSF) prophylaxis

Primary prophylaxis is NOT indicated

See Chapter 43 for more information

Antimicrobial prophylaxis

Risk of fever and neutropenia is LOW

Antimicrobial primary prophylaxis to be considered:

Antibacterial—not indicated
Antifungal—not indicated
Antiviral—not indicated unless patient previously had an episode of HSV

See Chapter 47 for more information

Patient Population Studied

A multicenter, nonrandomized, phase 2 study involved 92 patients with histologically confirmed, locally advanced squamous and adenosquamous cervical cancer. Eligible patients were aged >18 years, with an Eastern Cooperative Oncology Group (ECOG) performance status score ≤1. All patients received 40 mg/m² cisplatin in 500 mL of sodium chloride solution intravenously over 1 hour and 2 mg/m² topotecan in 100 mL of 5% dextrose in water intravenously over 30 minutes on days 1, 8, and 15 of a 28-day cycle for 2 courses. Patients were premedicated with 8 mg ondansetron and 20 mg dexamethasone, given intravenously 30 minutes before each course

Efficacy (N = 92)

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Clinical response rate^✫

77%

Pathologic response rate^†

67%

Median time to relapse

22 months

Disease-free survival at 2 years

76%

Overall survival at 2 years

86%

^✫Clinical response rate is the percentage of patients who experienced a partial or complete response according to the Response Criteria in Solid Tumours (RECIST) 1.0 guidelines

^†Pathological response rate is the percentage of patients who experienced a microscopic partial response or a complete response according to the TNM classification

Note: Median follow-up time was 18 months

Therapy Monitoring

Once per week: CBC with differential and platelet count
Before the start of a cycle: CBC with differential, serum electrolytes, calcium, magnesium, BUN, and creatinine

Treatment Modifications

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TOPOTECAN + CISPLATIN DOSE MODIFCIATIONS

Starting topotecan dose

2 mg/m²

Topotecan dose level −1

1.6 mg/m²

Topotecan dose level −2

1.25 mg/m²

Starting cisplatin dose

40 mg/m²

Cisplatin dose level −1

30 mg/m²

Cisplatin dose level −2

20 mg/m²

Adverse Events

Treatment Modifications

Day of treatment (day 1, 8, or 15) ANC <1000/mm³ or platelets <100,000/mm³

Delay both topotecan and cisplatin treatment by 1 week

Febrile neutropenia (ANC <1000/mm³ with temperature >38°C or >100.4°F), or ANC <1000/mm³ for ≥7 days

Reduce topotecan dose by 1 level and consider adding filgrastim in subsequent cycles, if applicable. Continue with same cisplatin dosage

Febrile neutropenia (ANC <1000/mm³ with temperature >38°C or >100.4°F), or ANC <1000/mm³ for ≥7 days despite 1 dose reduction

Administer filgrastim in subsequent cycles. If already administering filgrastim, reduce topotecan dosage by 1 level

Platelet nadir <50,000/mm³, or platelets <100,000/mm³ for ≥7 days

Reduce topotecan dose by 1 level; continue with same cisplatin dosage

G2 peripheral neuropathy

Reduce cisplatin dose by 2 dose levels; if neuropathy improves, can consider increasing by 1 dose level

G3/4 peripheral neuropathy

Hold cisplatin until neuropathy G1; then reduce cisplatin dosage by 2 levels. If G3/4 toxicity persists >2 weeks beyond scheduled start of next cycle, discontinue cisplatin

Day of treatment (day 1, 8, or 15) serum creatinine ≥1.5 mg/dL

Ensure patient adequately hydrated. Hold cisplatin until serum creatinine ≤1.5 mg/dL (≤133 µmol/L); then resume treatment at same dose or 1 dose level lower. If creatinine >1.5 mg/dL >2 weeks beyond scheduled start of next cycle, discontinue cisplatin

G1 tinnitus

Reduce cisplatin dose by 1 level

≥G2 tinnitus or hearing loss

Hold cisplatin until ototoxicity ≤G1; then reduce cisplatin dosage by 2 levels. If G2–4 toxicity persists >2 weeks beyond scheduled start of next cycle, discontinue cisplatin

G2/3 mucositis or diarrhea

Reduce topotecan dosage by 1 level

G4 mucositis or diarrhea

Reduce topotecan dosage by 1–2 levels

Recurrent mucositis or diarrhea despite dosage reduction or persistence of mucositis/diarrhea >2 weeks beyond scheduled start of next cycle

Discontinue topotecan

Other G3/4 nonhematologic toxicity

Delay attributable medication(s) until resolution to ≤G1, then reduce dose of attributable medication(s) by 1 level

Topotecan dose adjustments for renal impairment [likely to be superseded by cisplatin]

Creatinine clearance 46–60 mL/min: reduce topotecan dose by 20%
Creatinine clearance 31–45 mL/min: reduce topotecan dose by 25%
Creatinine clearance ≤30 mL/min: reduce topotecan dose by 30%

Adverse Events (N = 92)

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Grade (%)^✫

Grade 1/2

Grade 3/4

Neutropenia

Anemia

Gastrointestinal

Thrombocytopenia

Alopecia

^✫According to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0

Notes: All observed toxicities are included in the table. No treatment-related deaths occurred. Grade 3/4 adverse events occurred in 28% of patients and 5% of courses

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Vaginal Cancer Regimen: Topotecan + Cisplatin (Topocis)

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