title: Neo-adjuvant chemo-(immuno-)therapy of advanced squamous-cell head and neck carcinoma: a multicenter, phase III, randomized study comparing cisplatin + 5-fluorouracil (5-FU) with cisplatin + 5-FU + recombinant interleukin 2.
abstract: We carried out an open, randomized, phase III, multicenter clinical trial to compare, in neo-adjuvant setting, the clinical response and toxicity of the combination chemotherapy cisplatin + 5-FU with the same combination plus s.c. recombinant interleukin-2 (rIL-2) in patients with advanced (stage III IV) head and neck squamous-cell carcinoma (HNSCC). Regimen A was the classical Al Sarraf treatment: 100 mg/m2 cisplatin i.v. on day 1 plus 1000 mg m(-2) day(-1) 5-FU on days 1-5 as a continuous infusion. Regimen B was the same as regimen A plus 4.5 MIU/day rIL-2 s.c. on days 8-12 and 15-19. Treatment was repeated every 3 weeks for three cycles. A total of 33 patients were enrolled in the study; 30 were evaluable for toxicity and 28 for response. Seventeen patients were assigned to group A and 16 were assigned to group B. Three patients (20%) of group A and 4 (31%) of group B had a complete response, 9 patients (60%) of group A and 6 (46%) of group B had a partial response, with an overall response rate of 12 patients (80%) for group A and 10 patients (77%) for group B. Two patients (13%) of group A and 3 patients (23%) group B had stable disease; 1 patient (7%) of group A had progressive disease. Thus, there was not a statistically significant difference in response rate between the two groups and therefore there was no benefit from the addition of immunotherapy with rIL-2 to the standard chemotherapy. Both regimens were well tolerated. There were 2 toxic deaths (6.7%), 1 from hematological causes in group A and I from cardiac causes in group B. Myelosuppression and gastrointestinal toxicity, mainly nausea/vomiting and stomatitis, were the most frequent toxicities. The calculated number of patients for the sample has not yet been reached; however, the projection of our present results suggests that it is highly improbable that a clinically significant difference between the two treatment groups will be observed even if the calculated patient sample size is achieved.
authors.affiliation: Department of Medical Oncology, University of Cagliari, Italy. mantovan@pacs.unica.it
authors.forename: G
authors.initials: G
authors.lastname: Mantovani
authors.forename: V
authors.initials: V
authors.lastname: Gebbia
authors.forename: M
authors.initials: M
authors.lastname: Airoldi
authors.forename: C
authors.initials: C
authors.lastname: Bumma
authors.forename: P
authors.initials: P
authors.lastname: Contu
authors.forename: A
authors.initials: A
authors.lastname: Bianchi
authors.forename: M
authors.initials: M
authors.lastname: Ghiani
authors.forename: D
authors.initials: D
authors.lastname: Dessì
authors.forename: E
authors.initials: E
authors.lastname: Massa
authors.forename: L
authors.initials: L
authors.lastname: Curreli
authors.forename: B
authors.initials: B
authors.lastname: Lampis
authors.forename: P
authors.initials: P
authors.lastname: Lai
authors.forename: C
authors.initials: C
authors.lastname: Mulas
authors.forename: A
authors.initials: A
authors.lastname: Testa
authors.forename: E
authors.initials: E
authors.lastname: Proto
authors.forename: G
authors.initials: G
authors.lastname: Cadeddu
authors.forename: G
authors.initials: G
authors.lastname: Tore
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality; D002945:Cisplatin / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use*; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D007376:Interleukin-2 / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D007376:Interleukin-2; D011994:Recombinant Proteins; C082598:aldesleukin; D002945:Cisplatin; D005472:Fluorouracil