[Adjuvant adoptive immunotherapy in patients with stage III and resected stage IV melanoma: a pilot study].
Adoptive immunotherapy trials with tumor infiltrating lymphocytes (TIL) and interleukin-2 (IL-2) were carried out in the treatment of advanced melanoma with a 34% of overall responses (OR). However, theoretically it should be of greater benefit as adjuvant therapy, especially in high-risk stages (stage III and resected stage IV). In a pilot study, 22 patients (aged 23-72 years) with stage III-IV melanoma who underwent radical metastasectomy were reinfused with TIL cultivated and expanded in vitro with IL-2 from surgically removed metastases. IL-2 (starting dose 12 x 10(6) IU/m2) was co-administered as a continuous infusion according to West's scheme. A total of 8/22 (36.3%) patients were disease-free (DF) at a median follow-up of 5 years. DF survival (DFS) and overall survival (OS) in the remaining 14 patients were 44% and 37% and 52% and 45% at 2 and 3 years, respectively. The CNS was the only site of disease recurrence in 57% of patients who relapsed. DF patients received a higher median dose of IL-2 than those who progressed (total dose 110 x 10(6) vs 86 x 10(6) IU/m2, respectively). The progressive reduction in IL-2 dosage allowed all patients to complete treatment without permanent grade 4 toxicity. The effects of tumor immunosuppression in lymphocytes inside the tumor (TCR z and e chains, p56lck, FAS and FAS-ligand) confirmed that the potential function of TIL, immunodepressed at the time of metastasectomy, was significantly restored after in vitro, culture with IL-2. Adjuvant adoptive immunotherapy with TIL and IL-2 seems to improve DFS and OS, in comparison with literature data. Further studies are required to determine its role in the adjuvant treatment of patients with high-risk melanoma.
Verdecchia
G M
GM
Istituto Oncologico Romagnolo (IOR), Forli.
Ridolfi
L
L
Ridolfi
R
R
Riccobon
A
A
Bertagni
A
A
Vagliasindi
A
A
Petrini
M
M
Stefanelli
M
M
Milandri
C
C
Amadori
D
D
D000328:Adult; D000368:Aged; D002478:Cells, Cultured / Q000187:drug effects / Q000637:transplantation; D016543:Central Nervous System Neoplasms / Q000556:secondary; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016219:Immunotherapy, Adoptive; D007376:Interleukin-2 / Q000494:pharmacology; D008175:Lung Neoplasms / Q000556:secondary; D008207:Lymphatic Metastasis; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects / Q000637:transplantation*; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000556:secondary / Q000601:surgery / Q000628:therapy*; D008875:Middle Aged; D009367:Neoplasm Staging; D010865:Pilot Projects; D012878:Skin Neoplasms / Q000276:immunology / Q000556:secondary / Q000601:surgery / Q000628:therapy*; D016019:Survival Analysis; D016896:Treatment Outcome
D007376:Interleukin-2