| General information |
| Database: | DB00674 |
| Objective: | The aim of the study was to determine whether the addition of gefitinib to RT and gemcitabine for patients with locally advanced pancreatic carcinoma (LAPC) was feasible and safe. |
| Authors: | Maurel J, et al |
| Title: | Phase I trial of gefitinib with concurrent radiotherapy and fixed 2h gemcitabine infusion, in locally advanced pancreatic cancer. |
| Journal: | Int J Radiat Oncol Biol Phys |
| Year: | 2006 |
| PMID: | 16965868 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | gefitinib
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | pancreatic cancer |
| Cancer Subtype: | PANCREATIC CANCER |
| Therapy Type: | com |
| Therapeutic Combination Type: | 3 |
| Therapeutic Combination Content: | gefitinib with concurrent radiotherapy and fixed 2h gemcitabine infusion |
| Study Type: | phase I study |
| Key Patients Feature: | Eastern Cooperative Oncology Group (ECOG) performance status 1, age 18 years, absolute granulocyte count 1500/mm3, platelet count 100, 000/mm3, 24h creatinine clearance 45 ml/min, bilirubin 2.5 mg/dl upper limit of normal, aspartate aminotransferase andalanine aminotransferase 2.5 upper limit of normal, no priorradiotherapy and chemotherapy, PTV 500 cm3 excluding prophylactic regional node irradiation, no malignancy other thancuratively treated carcinoma in situ of the cervix or basal cellcarcinoma of the skin, and no serious medical or psychiatric illnessthat would preclude informed consen |
| Biomarker: | levels of plasma VEGF and IL8 |
| Biomark Analysis: | No significant reduction of vascular endothelial growth factor and interleukin8 was observed after treatment. |
| Control Group Info: | single arm |
| Treatment Info: | An initial cohort of 6 patients was treated with RT (45 Gy/25 fractions/5 weeks) plus concomitant gefitinib (250 mg/day). Successive cohorts of patients received 100, 150, and 200 mg/m(2)/day of gemcitabine in a 2h infusion over weeks 1, 2, 3, 4, and 5 with gefitinib (250 mg/day) and RT. Gefitinib was continued after RT until progression. A pharmacodynamic study of angiogenic markers was also performed to evaluate a possible antiangiogenic effect. |
| Primary End Point: | DLT, MDT, and toxicities |
| Secondary End Point: | NA |
| Patients Number: | 18 |
| Trial Results |
| DLT_MTD: | There were no doselimiting toxicities MTD of gemcitabine was not reached in our series |
| Objective Response Rate: | Of the 18 patients enrolled onto the protocol, 3 died before being evaluated for radiologic response. One of theremaining 15 patients had a radiographically documentedresponse to therapy, assessed by CT after completion of treatment. All 18 patients were evaluated for CA.19.9. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 3.7 months (95% CI 1.9-5.5) |
| Median OS A vs. C: | 7.5 months(95% CI 5.2-9.9) |
| Adverse Event(agent arm): | There were no doselimiting toxicities. Common toxicities were mild neutropenia, asthenia, diarrhea, cutaneous rash and nausea/vomiting. |
| Conclusions: | Their results support that the combination of gefitinib, RT, and gemcitabine has an acceptable toxicity but with modest activity in LAPC. |