Lack in efficacy for imatinib mesylate as second-line treatment of recurrent or metastatic cervical cancer expressing platelet-derived growth factor receptor alpha.
Imatinib mesylate inhibits platelet-derived growth factor receptor (PDGFR), and there are evidences that the PDGFR participates in development and progression of cervical cancer. This pilot study was set to evaluate the efficacy in response rate and progression-free survival of imatinib. A secondary end point was to evaluate its safety as second-line treatment of recurrent or metastatic cervical cancer expressing PDGFRalpha. Imatinib mesylate was administered in daily dosages of 600 mg. Response was evaluated by positron emission tomography/computed tomography every two 28-day courses, and toxicity was evaluated weekly and thereafter. Twelve patients were included in the study. The median age was 49.8 years; all but 1 tumor were squamous cell carcinomas. First-line palliative chemotherapy with carboplatin-paclitaxel was the most frequently used scheme (75.0%). Ten (83.3%) had pelvic and systemic disease, whereas only 2 had systemic disease alone. All patients expressed the PDGFRalpha in more than 10% of malignant cells, whereas only 4 coexpressed the PDGFRbeta. No patient showed response. A single patient having metastatic disease in the lung showed stabilization for 6 months to then progressing in bone. No severe toxicities were seen except for the patient with worsening of bleeding from proctitis. Grades 1 and 2 gastrointestinal toxicities were common. Despite lack of activity of single-agent imatinib, further studies in cervical cancer are deserved to better define the status of imatinib targets in this tumor and to investigate its activity in combination with cytotoxic drugs.
Candelaria
Myrna
M
Division of Clinical Research, UNAM/Instituto Nacional de Cancerología, Mexico City, Mexico.
Arias-Bonfill
Daymi
D
Chávez-Blanco
Alma
A
Chanona
José
J
Cantú
David
D
Pérez
Cetina
C
Dueñas-González
Alfonso
A
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001549:Benzamides; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism*; D012008:Recurrence; D016019:Survival Analysis; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D020796:Receptor, Platelet-Derived Growth Factor alpha