[Evaluation of irinotecan hydrochloride (CPT-11) and trastuzumab combination therapy as salvage treatment in patients with HER2 overexpressing metastatic breast cancer].
BACKGROUND
Though irinotecan hydrochloride(CPT-11)was approved in Japan in 1994, there have been few reports since that evaluated the efficacy of CPT-11. The position of this agent in the treatment of patients with metastatic breast cancer(MBC)is not definite. In addition, no report has been published to date about CPT-11 and trastuzumab combination therapy.


OBJECTIVE
To evaluate retrospectively the efficacy of CPT-11 and trastuzumab combination therapy as salvage treatment in patients with human epidermal growth factor receptor 2 (HER2)overexpressing MBC.


METHODS
We examined ten cases who received this therapy against MBC since February 2002 till March 2007 in our hospital. Overall response rate, change of tumor markers, time to treatment failure (TTF), time to progression( TTP), overall survival (OS)after start of CPT-11 and adverse events were examined for efficacy and tolerability.


RESULTS
Median age was 57 (40-67)and median number of prior chemotherapies was 5(2-9). Though the overall response rate was 20%, some tumor reduction was observed totally in seven cases. CEA and CA15-3 were decreased in 78%(7/9)and 63%(5/8) of cases, respectively. Median TTF, TTP and OS were 3, 4, and 6 months, respectively. Adverse events included three cases of severe neutropenia, one of whom died of treatment-related sepsis. Slight diarrhea occurred in seven and severe nausea occurred in two cases. Dose modification of CPT-11 was necessary in 5 cases, and three discontinued CPT-11 administration, mainly due to easy fatigability, nausea and neutropenia. During the therapy, four cases were all inpatients, and 6 eventually became outpatients.


CONCLUSIONS
This therapy for patients with HER2 overexpressing metastatic cancer resistant to multi-agents demonstrated a good result in terms of antitumor effect. But high tolerability could not be documented by our experience with this therapy. It was supposed that the risk management with prediction of adverse events and preparation of better supportive therapy could make for the higher tolerability of this therapy for more effective clinical use.
Ikeda
Masahiko
M
Dept. of Breast and Thyroid Surgery, Kawasaki Medical School.
Kurebayashi
Junichi
J
Sonoo
Hiroshi
H
Oota
Yusuke
Y
Fujii
Sayaka
S
Shimo
Toshirou
T
Miyake
Akiko
A
Seki
Mari
M
Souda
Mai
M
Nomura
Tsunehisa
T
Yamamoto
Yutaka
Y
Shiiki
Shigeo
S
Nakashima
Kazutaka
K
Tanaka
Katsuhiro
K
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D018450:Disease Progression; D006801:Humans; D007167:Immunotherapy; D000077146:Irinotecan; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy / Q000473:pathology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D016879:Salvage Therapy; D015996:Survival Rate; D000068878:Trastuzumab; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D002166:Camptothecin; D000077146:Irinotecan; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab