Concurrent liposomal cisplatin (Lipoplatin), 5-fluorouracil and radiotherapy for the treatment of locally advanced gastric cancer: a phase I/II study.
OBJECTIVE
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
Lipoplatin was given at a dose of 120 mg/m(2)/week, 5-fluorouracil at 400mg/m(2)/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.
Koukourakis
Michael I
MI
Departments of Radiotherapy/Oncology, Pathology and Surgery, Democritus University of Thrace, Alexandroupolis, Greece.
Giatromanolaki
Alexandra
A
Pitiakoudis
Michael
M
Kouklakis
George
G
Tsoutsou
Pelagia
P
Abatzoglou
Ioannis
I
Panteliadou
Marianthi
M
Sismanidou
Kyriaki
K
Sivridis
Efthimios
E
Boulikas
Teni
T
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy / Q000009:adverse effects / Q000379:methods; D004334:Drug Administration Schedule; D005221:Fatigue / Q000209:etiology; D005240:Feasibility Studies; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000528:radiation effects; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000209:etiology; D011836:Radiation Tolerance; D011879:Radiotherapy Dosage; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*
C503131:lipoplatin; D002945:Cisplatin; D002955:Leucovorin; D005472:Fluorouracil