A phase I study of weekly doxorubicin and oral topotecan for patients with relapsed or refractory small cell lung cancer (SCLC): A Fred and Pamela Buffet Cancer Center Clinical Trials Network study

Vinicius Ernani, Rahat Jahan, Lynette M. Smith, Alissa S. Marr, Sarah E. Kimbrough, Mary E. Kos, Jolene Tijerina, Shannon Pivovar, Imayavaramban Lakshmanan, Marsha Ketcham, Sanchita Rauth, Kavita Mallya, Mohd W. Nasser, Maneesh Jain, Anne Kessinger, Surinder K. Batra, Apar Kishor Ganti

Research output: Contribution to journalArticle


Background: Relapsed/refractory small cell lung cancer (SCLC) has a poor prognosis, with no good options. We evaluated a novel combination of topotecan and doxorubicin, providing sequential topoisomerase I and II inhibition, in this setting. Materials and methods: Adult patients (>19 years) with relapsed/refractory SCLC, who had received at least one prior chemotherapy regimen were eligible. Patients received escalating doses of oral topotecan on days 1–5 of each three week cycle (maximum - 5 cycles). The dosing cohorts were: 0.85 mg/m2, 1.05 mg/m2, 1.35 mg/m2, 1.65 mg/m2 and 2.30 mg/m2. All patients received weekly doxorubicin 20 mg/m2 intravenously starting day 6 of the first cycle and continued weekly for a maximum of 15 weeks. In the absence of pre-specified dose limiting toxicities (DLT), patients were enrolled serially to escalated dose level cohorts. Results: Twenty-two patients were enrolled, of which 20 were evaluable. Median age was 61 years; 74% were male and 95% were Caucasian. Hematologic side effects were the most common adverse events. There were no therapy-related Grade 5 toxicities. Incidence of DLT based on cohorts were: DL2: 1/6 (Grade 4 thrombocytopenia), DL3: 1/6 (AST elevation) and DL4: 2/4 (Grade 4 thrombocytopenia). Response rate was 20% (4/20) and disease control rate (SD + PR) was 36%. The median progression free and overall survival were 3.6 months and 6 months, respectively. Conclusions: The combination of topotecan and doxorubicin was safe and effective in relapsed/refractory SCLC. The maximum tolerated dose of oral topotecan was 1.35 mg/m2 when given concurrently with weekly doxorubicin.

Original languageEnglish (US)
Article number100162
JournalCancer Treatment and Research Communications
StatePublished - 2020



  • Doxorubicin
  • Phase 1 clinical trial
  • Small cell lung cancer
  • Topoisomerase 2
  • Topoisomerase1
  • Topotecan

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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