TY - JOUR
T1 - A systematic review on topoisomerase 1 inhibition in the treatment of metastatic breast cancer
AU - Kümler, Iben
AU - Brünner, Nils
AU - Stenvang, Jan
AU - Balslev, Eva
AU - Nielsen, Dorte L.
PY - 2013/4
Y1 - 2013/4
N2 - Following treatment with anthracyclines and taxanes, few established options exist for the treatment of metastatic breast cancer (MBC). Although the topoisomerase 1 inhibitors irinotecan, etirinotecan, and topotecan have been used in clinical trials on MBC, the drugs have never been introduced as standard treatment for the disease. We performed a systematic review on topoisomerase 1 inhibitors in MBC and found 22 prospective trials and three retrospective ones. No phase III trials were identified. Only one study was randomized, and generally studies were small. Response rates (RR) for irinotecan monotherapy varied from 5 to 23 %, whereas RRs for etirinotecan were 26-32 %. Only four trials on topotecan monotherapy were reported with RRs of 6-31 %. Combination therapy with irinotecan and various chemotherapeutics resulted in RRs ranging from 14 to 64 %, whereas irinotecan combined with biologic agents showed very limited effect. Topotecan was studied in combination with either another chemotherapeutic or a biologic agent in two trials, both studies failing to show any effect of topotecan. The most common grade 3 and 4 adverse events (AE) for irinotecan were neutropenia, diarrhea, and nausea/vomiting. The dosing schedule appears to affect the toxicity profile of the drug. Hematologic AEs are most frequently reported for topotecan. Conclusively, topotecan does not seem to be efficient in the treatment of MBC. Irinotecan seem to be effective in some patients previously treated with anthracyclines and taxanes. RRs of 23 % for irinotecan and 32 % for etirinotecan are comparable to some of the more commonly used treatments for MBC. However, a large proportion of patients do not respond, thus emphasizing the need for a biomarker predictive of response to irinotecan in order to introduce this drug as the standard treatment for MBC.
AB - Following treatment with anthracyclines and taxanes, few established options exist for the treatment of metastatic breast cancer (MBC). Although the topoisomerase 1 inhibitors irinotecan, etirinotecan, and topotecan have been used in clinical trials on MBC, the drugs have never been introduced as standard treatment for the disease. We performed a systematic review on topoisomerase 1 inhibitors in MBC and found 22 prospective trials and three retrospective ones. No phase III trials were identified. Only one study was randomized, and generally studies were small. Response rates (RR) for irinotecan monotherapy varied from 5 to 23 %, whereas RRs for etirinotecan were 26-32 %. Only four trials on topotecan monotherapy were reported with RRs of 6-31 %. Combination therapy with irinotecan and various chemotherapeutics resulted in RRs ranging from 14 to 64 %, whereas irinotecan combined with biologic agents showed very limited effect. Topotecan was studied in combination with either another chemotherapeutic or a biologic agent in two trials, both studies failing to show any effect of topotecan. The most common grade 3 and 4 adverse events (AE) for irinotecan were neutropenia, diarrhea, and nausea/vomiting. The dosing schedule appears to affect the toxicity profile of the drug. Hematologic AEs are most frequently reported for topotecan. Conclusively, topotecan does not seem to be efficient in the treatment of MBC. Irinotecan seem to be effective in some patients previously treated with anthracyclines and taxanes. RRs of 23 % for irinotecan and 32 % for etirinotecan are comparable to some of the more commonly used treatments for MBC. However, a large proportion of patients do not respond, thus emphasizing the need for a biomarker predictive of response to irinotecan in order to introduce this drug as the standard treatment for MBC.
KW - Antineoplastic Combined Chemotherapy Protocols
KW - Breast Neoplasms
KW - Camptothecin
KW - Clinical Trials as Topic
KW - DNA Topoisomerases, Type I
KW - Female
KW - Humans
KW - Neoplasm Metastasis
KW - Topoisomerase I Inhibitors
KW - Topotecan
KW - Treatment Outcome
KW - Tumor Markers, Biological
KW - Metastatic breast cancer
KW - Topoisomerase 1
KW - inhibitors
KW - Treatment
KW - Systematic review
U2 - 10.1007/s10549-013-2476-3
DO - 10.1007/s10549-013-2476-3
M3 - Journal article
C2 - 23512247
SN - 0167-6806
VL - 138
SP - 347
EP - 358
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
IS - 2
ER -
