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

Abstract

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
Volume22
DOIs
StatePublished - 2020

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Topotecan
Small Cell Lung Carcinoma
Doxorubicin
Clinical Trials
Neoplasms
Type II DNA Topoisomerase
Type I DNA Topoisomerase
Maximum Tolerated Dose
Disease-Free Survival
Drug Therapy
Incidence

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

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

In: Cancer Treatment and Research Communications, Vol. 22, 100162, 2020.

Research output: Contribution to journalArticle

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title = "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",
abstract = "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.",
keywords = "Doxorubicin, Phase 1 clinical trial, Small cell lung cancer, Topoisomerase 2, Topoisomerase1, Topotecan",
author = "Vinicius Ernani and Rahat Jahan and Smith, {Lynette M.} and Marr, {Alissa S.} and Kimbrough, {Sarah E.} and Kos, {Mary E.} and Jolene Tijerina and Shannon Pivovar and Imayavaramban Lakshmanan and Marsha Ketcham and Sanchita Rauth and Kavita Mallya and Nasser, {Mohd W.} and Maneesh Jain and Anne Kessinger and Batra, {Surinder K.} and Ganti, {Apar Kishor}",
year = "2020",
doi = "10.1016/j.ctarc.2019.100162",
language = "English (US)",
volume = "22",
journal = "Cancer Treatment and Research Communications",
issn = "2213-0896",
publisher = "Elsevier Ltd",

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TY - JOUR

T1 - A phase I study of weekly doxorubicin and oral topotecan for patients with relapsed or refractory small cell lung cancer (SCLC)

T2 - A Fred and Pamela Buffet Cancer Center Clinical Trials Network study

AU - Ernani, Vinicius

AU - Jahan, Rahat

AU - Smith, Lynette M.

AU - Marr, Alissa S.

AU - Kimbrough, Sarah E.

AU - Kos, Mary E.

AU - Tijerina, Jolene

AU - Pivovar, Shannon

AU - Lakshmanan, Imayavaramban

AU - Ketcham, Marsha

AU - Rauth, Sanchita

AU - Mallya, Kavita

AU - Nasser, Mohd W.

AU - Jain, Maneesh

AU - Kessinger, Anne

AU - Batra, Surinder K.

AU - Ganti, Apar Kishor

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

KW - Doxorubicin

KW - Phase 1 clinical trial

KW - Small cell lung cancer

KW - Topoisomerase 2

KW - Topoisomerase1

KW - Topotecan

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U2 - 10.1016/j.ctarc.2019.100162

DO - 10.1016/j.ctarc.2019.100162

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JO - Cancer Treatment and Research Communications

JF - Cancer Treatment and Research Communications

SN - 2213-0896

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