Concurrent Liposomal Cisplatin (Lipoplatin), 5-Fluorouracil and Radiotherapy for the Treatment of Locally Advanced Gastric Cancer: A Phase I/II Study

• Published in: International journal of radiation oncology, biology, physics Vol. 78; no. 1; pp. 150 - 155
• Main Authors: Koukourakis, Michael I., M.D, Giatromanolaki, Alexandra, M.D, Pitiakoudis, Michael, M.D, Kouklakis, George, M.D, Tsoutsou, Pelagia, M.D, Abatzoglou, Ioannis, Ph.D, Panteliadou, Marianthi, M.D, Sismanidou, Kyriaki, M.Sc, Sivridis, Efthimios, M.D, Boulikas, Teni, M.D
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.09.2010; Elsevier
• Subjects: Aged; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; AZINES; Biological and medical sciences; BODY; CHEMOTHERAPY; Cisplatin - administration & dosage; Cisplatin - adverse effects; Combined Modality Therapy - adverse effects; Combined Modality Therapy - methods; COMPUTERIZED TOMOGRAPHY; DIAGNOSTIC TECHNIQUES; DIGESTIVE SYSTEM; DISEASES; Drug Administration Schedule; DRUGS; Fatigue - etiology; Feasibility Studies; Female; Fluorouracil - administration & dosage; Fluorouracil - adverse effects; Gastric cancer; Gastroenterology. Liver. Pancreas. Abdomen; GASTROINTESTINAL TRACT; Hematology, Oncology and Palliative Medicine; HETEROCYCLIC COMPOUNDS; Humans; HYDROXY COMPOUNDS; Kidney - drug effects; Kidney - radiation effects; Leucovorin - administration & dosage; Lipoplatin; Liposomal cisplatin; LIPOSOMES; Male; Medical sciences; MEDICINE; Middle Aged; NEOPLASMS; Neutropenia - etiology; NUCLEAR MEDICINE; ORGANIC COMPOUNDS; ORGANIC NITROGEN COMPOUNDS; ORGANS; Pharmacology. Drug treatments; PYRIMIDINES; Radiation Tolerance; RADIOLOGY; RADIOLOGY AND NUCLEAR MEDICINE; RADIOTHERAPY; Radiotherapy Dosage; STOMACH; Stomach Neoplasms - drug therapy; Stomach Neoplasms - pathology; Stomach Neoplasms - radiotherapy; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; THERAPY; TOMOGRAPHY; Tumors; URACILS; Chemotherapy; Lipoplatin; Radiotherapy; Gastric cancer; Liposomal cisplatin; Antineoplastic agent; Stomach cancer; Phase II trial; Gastric disease; Platinum II Complexes; Fluorouracil; Enzyme; Fluoropyrimidine derivatives; Transferases; Enzyme inhibitor; Liposome; Malignant tumor; Thymidylate synthase; Cisplatin; Alkylating agent; Treatment; Antimetabolic; Methyltransferases; Phase I trial; Pyrimidine derivatives; Digestive diseases; Cancer
• ISSN: 0360-3016; 1879-355X
• DOI: 10.1016/j.ijrobp.2009.07.1733

Purpose Liposomal drugs have a better tolerance profile and are highly accumulated in the tumor environment, properties that promise an optimal radiosensitization. We investigated the feasibility of the combination of 5-fluorouracil/lecovorin–based radio-chemotherapy with the administration of high weekly dose of a liposomal platinum formulation (Lipoplatin™). Methods and Materials Lipoplatin was given at a dose of 120mg/m2 /week, 5-fluorouracil at 400mg/m2 /week (Day 1), whereas radiotherapy was given through 3.5-Gy fractions on Days 2, 3, and 4. Two groups of 6 patients received four and five consecutive cycles, respectively. Results Minimal nephrotoxicity (18.2% Grade 1) and neutropenia (9% Grade 3) was noted. Fatigue Grade 2 appeared in 25% of cases. Abdominal discomfort was reported by 18% of patients. No liver, kidney, gastric, or intestinal severe acute or late sequellae were documented, although the median follow-up of 9 months is certainly too low to allow safe conclusions. A net improvement in the performance status (from a median of 1 to 0) was recorded 2 months after the end of therapy. The response rates assessed with computed tomography, endoscopy, and biopsies confirmed 33% (2 of 6) tumor disappearance in patients treated with four cycles, which reached 80% (4 of 5) in patients receiving five cycles. Conclusions Lipoplatin radio-chemotherapy is feasible, with minor hematological and nonhematological toxicity. The high complete response rates obtained support the testing of Lipoplatin in the adjuvant postoperative or preoperative radio-chemotherapy setting for the treatment of gastric cancer.