Successful chemotherapeutic modality of doxorubicin plus dacarbazine for the treatment of desmoid tumors in association with familial adenomatous polyposis.
OBJECTIVE
Desmoid tumors are locally aggressive and can be fatal in familial adenomatous polyposis (FAP) patients if they are not suitable for surgery or radiation therapy. Here, we prospectively investigated the efficacy of a chemotherapeutic regimen involving doxorubicin (DOX) and dacarbazine (DTIC) for inoperable FAP-associated desmoid tumors.


METHODS
From an initial group of 120 FAP patients, seven of the 11 individuals with symptomatic unresectable desmoid tumors that were unresponsive to conventional hormone therapy were enrolled onto this study. The general chemotherapy regimen comprised four or five cycles of DOX (20 mg/m2 daily) plus DTIC (150 mg/m2 daily) throughout 4 days of drip intravenous infusion (day 1 through 4) every 28 days, followed by the cyclooxygenase-2 inhibitor meloxicam (10 mg/m2). The primary end point was relapse-free survival. The secondary end points included toxicity, clinical improvement, and tumor regression according to computed tomography.


RESULTS
Significant tumor regression was observed clinically and radiologically in all seven patients. Three patients showed a complete response. The average progression-free survival period was 74.0 months (range, 32.5 to 107.5 months). Three patients showed grade 3 adverse events with no treatment-related mortality. All seven patients survived and remained without tumor progression. An adenomatous polyposis coli germline-mutation analysis revealed no mutations in the specified regions.


CONCLUSIONS
A chemotherapeutic regimen of DOX plus DTIC followed by meloxicam is an effective and safe treatment for FAP-associated desmoid tumors. This modality should be considered for use as first-line chemotherapy in symptomatic desmoid tumors that are unresponsive to conventional medical therapy, due to the absence of useful presymptomatic markers.
Gega
Makoto
M
Second Department of Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
Yanagi
Hidenori
H
Yoshikawa
Reigetsu
R
Noda
Masafumi
M
Ikeuchi
Hiroki
H
Tsukamoto
Kiyoshi
K
Oshima
Tsutomu
T
Fujiwara
Yoshinori
Y
Gondo
Nobuhisa
N
Tamura
Kazuo
K
Utsunomiya
Joji
J
Hashimoto-Tamaoki
Tomoko
T
Yamamura
Takehira
T
D011125:Adenomatous Polyposis Coli / Q000188:drug therapy* / Q000401:mortality; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003606:Dacarbazine / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D018222:Desmoid Tumors / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000401:mortality; D017491:Genes, APC; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D000077239:Meloxicam; D012189:Retrospective Studies; D013843:Thiazines / Q000008:administration & dosage; D013844:Thiazoles / Q000008:administration & dosage; D014057:Tomography, X-Ray Computed
D013843:Thiazines; D013844:Thiazoles; D003606:Dacarbazine; D004317:Doxorubicin; D000077239:Meloxicam