Phase I trial of gefitinib with concurrent radiotherapy and fixed 2-h gemcitabine infusion, in locally advanced pancreatic cancer

Journal Article · Fri Dec 01 04:00:00 EST 2006 · International Journal of Radiation Oncology, Biology and Physics

DOI:https://doi.org/10.1016/j.ijrobp.2006.07.008· OSTI ID:20850262

Maurel, Joan ^[1]; Martin-Richard, Marta ^[2]; Conill, Carlos ^[3]; Sanchez, Marcelo ^[4]; Petriz, Lourdes ^[5]; Gines, Angels ^[6]; Miquel, Rosa ^[7]; Gallego, Rosa ^[1]; Cajal, Rosana ^[8]; Ayuso, Carmen ^[4]; Navarro, Salvador; Marmol, Maribel; Nadal, Cristina; Auge, Josep Maria; Gascon, Pere; Fernandez-Cruz, Laureano ^[9]

---

1. Medical Oncology Dept., Hospital Clinic, Institut de Investigacions Biomediques Cientifiques Agusti Pi I Suryer (IDIBAPS), University of Barcelona, Barcelona, Catalonia (Spain)
2. Medical Oncology Dept., Hospital Sant Pau, Barcelona, Catalonia (Spain)
3. Radiotherapy Dept., Hospital Clinic, Institut de Investigacions Biomediques Cientifiques Agusti Pi I Suryer (IDIBAPS), University of Barcelona, Barcelona, Catalonia (Spain)
4. Radiology Dept., Hospital Clinic, Institut de Investigacions Biomediques Cientifiques Agusti Pi I Suryer (IDIBAPS), University of Barcelona, Barcelona, Catalonia (Spain)
5. Radiotherapy Dept., Hospital Sant Pau, Barcelona, Catalonia (Spain)
6. Gastroenterology Dept., Hospital Clinic, Institut de Investigacions Biomediques Cientifiques Agusti Pi I Suryer (IDIBAPS), University of Barcelona, Barcelona, Catalonia (Spain)
7. Pathology Dept., Hospital Clinic, Institut de Investigacions Biomediques Cientifiques Agusti Pi I Suryer (IDIBAPS), University of Barcelona, Barcelona, Catalonia (Spain)
8. Medical Oncology Dept., Astra-Zeneca, Madrid (Spain)
9. Hospital Clinic, Institut de Investigacions Biomediques Cientifiques Agusti Pi I Suryer (IDIBAPS), University of Barcelona, Barcelona, Catalonia (Spain)

Purpose: Pancreatic cancers are resistant to radiotherapy (RT) and current chemotherapy agents. Epidermal growth factor receptor is overexpressed in pancreatic cancer, and in vitro studies have shown that epidermal growth factor receptor inhibitors can overcome radio- and chemoresistance. 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. Methods and Materials: Eighteen patients with pathologically proven LAPC, based on major vascular invasion based on helical computed tomography (CT) and endoscopic ultrasound, were entered into the study. The targeted irradiated volume included the tumor and 2-cm margin. Prophylactic irradiation of regional nodes was not allowed. Patients with >500 cm{sup 3} of planning tumor volume were excluded. 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{sup 2}/day of gemcitabine in a 2-h 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. Results: There were no dose-limiting toxicities. Common toxicities were mild neutropenia, asthenia, diarrhea, cutaneous rash and nausea/vomiting. The median (95% confidence interval [CI]) progression-free survival was 3.7 (95% CI = 1.9-5.5) months, and the median overall survival was 7.5 (95% CI 5.2-9.9) months. No significant reduction of vascular endothelial growth factor and interleukin-8 was observed after treatment. Conclusion: Our results support that the combination of gefitinib, RT, and gemcitabine has an acceptable toxicity but with modest activity in LAPC.

• OSTI ID: 20850262
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Journal Name: International Journal of Radiation Oncology, Biology and Physics Journal Issue: 5 Vol. 66; ISSN IOBPD3; ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
CARCINOMAS
CHEMOTHERAPY
COMPUTERIZED TOMOGRAPHY
DIARRHEA
GROWTH FACTORS
IN VITRO
INFUSION
IRRADIATION
NAUSEA
PANCREAS
PATIENTS
PLANNING
RADIATION DOSES
RADIOTHERAPY
RECEPTORS
TOXICITY
VOMITING