Target Therapy of Unresectable or Metastatic Dermatofibrosarcoma Protuberans With Imatinib Mesylate

Abstract

Dermatofibrosarcoma protuberans (DFSP) is a rare, plaque-like tumor of the cutaneous tissue occurring more on the trunk than the extremities and neck. More than 95% of DFSP present anomalies on the 17q22 and 22q13 chromosomal regions leading to the fusion of COL1A1 and PDGFB genes. Surgery is the optimal treatment for DFSP, but less effective in locally advanced or metastatic patients, as is the case with chemotherapy and radiotherapy. The aim of this study was to assess retrospectively the therapeutic activity and safety of imatinib on 22 Chinese patients with locally inoperative or metastatic DFSP at a single institution.In the collected data of 367 Chinese patients with DFSP, we analyzed retrospectively 22 patients with locally advanced or metastatic DFSP, all of whom received imatinib therapy at 1 center from January 2009 to October 2014. Patients were administered with imatinib at an initial dose of 400 mg and escalated to 800 mg daily after they developed imatinib resistance. The median follow-up time was 36 months, and the median treatment time was 15 months.The results showed that 10 locally advanced DFSP patients and 12 metastatic DFSP patients received imatinib therapy. Apart from 1 patient who developed primary imatinib resistance, 15 patients achieved partial remission (PR), and 6 patients achieved stable disease (SD). Both fibrosarcomatous DFSP and classic DFSP patients demonstrated similar response to imatinib. Median PFS was estimated to be 19 months. Median overall survival (OS) has not been reached, and estimated 1- and 3-year OS rates were 95.5% (21/22) and 77.3% (17/22), respectively. Four out of 10 patients with primarily unresectable DFSP received complete surgical resection after neoadjuvant treatment of imatinib.Imatinib therapy is well tolerated with a safety profile and is the therapy of choice in locally inoperative or metastatic DFSP. Neoadjuvant treatment of locally advanced or metastatic DFSP with imatinib improves surgical outcomes and may facilitate resection of difficult tumors.

Effectiveness of Imatinib Mesylate Treatment in a Patient with Dermatofibrosarcoma Protuberans with Pulmonary and Pancreatic Metastases

“…According to these clinical trials and molecular studies, imatinib has been approved for advanced and metastatic DFSP in approximately 60 countries, but not in Japan. The clinical outcomes of imatinib treatment for metastatic or advanced DFSP in Japanese cases that have been reported with English abstracts are summarized in Table. Although PDGFB fusion was not always consistent with a good response to imatinib, the obtained clinical outcomes were promising and similar to the results reported from other countries (12)(13)(14). Several clinical studies and case reports (3,(12)(13)(14)(15)(16)(17)(18) suggested that that a moderate dosage of 400-600 mg/day appeared to be as equally as effective as a higher dosage (800 mg/day) and was better tolerated.…”

“…The presence of the molecular target (COL1A1-PDGFB fusion) appears to be a marker of responsiveness to imatinib treatment in DFSP patients (12)(13)(14), although the response is not always consistent with the presence of COL1A1-PDGFB fusion. However, it has also been shown that FS-DFSP lacking the specific aberration does not respond to imatinib treatment (13,14). Thus, an examination of the presence of COL 1A1-PDGFB fusion in each case is critical before initiating imatinib therapy, as shown in the present case.…”

“…According to the pertinent literature, the major sites include the lungs, followed by the brain (5)(6)(7)(8)(9)(10)(11)(12)(13)(14). Pancreatic metastasis of DFSP is extremely rare, with only two other reported cases identified in the PubMed database using the search terms "DFSP" and "pancreas" or "distant metastasis" (9, 10).…”

“…Thus, imatinib therapy is a good option for unresectable, recurrent, or metastatic DFSP. Several clinical studies have demonstrated the efficacy of imatinib (12)(13)(14), however, little information is available regarding the usefulness of imatinib in Japanese patients with metastatic DFSP (15)(16)(17)(18). We encountered a case of abdominal wall DFSP that developed pulmonary and pancreatic metastases 5 years after complete resection.…”

Dermatofibrosarcoma Protuberans: A Rare Malignancy

“…Imatinib mesylate is also used in metastatic tumors in which resection is not possible or may have unacceptable functional and cosmetic results and radiotherapy cannot be performed. [12][13][14] This study aimed to review the literature for DFSP cases.…”