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.

The Role of Neck Dissection After Chemoradiotherapy for Oropharyngeal Cancer With Advanced Nodal Disease

“…Despite important advances in organ preservation and survival with platinum-based chemotherapy and radiotherapy, 11,12 the failure to achieve locoregional control remains a major cause of treatment failure and death in patients with locally advanced head and neck cancer. The role of neck dissection after chemoradiotherapy for head and neck cancer (eg, in respect to initial node stage and locoregional response 13,14 ) is unclear.…”

Covalent linking of proteins and cytokines to suture: Enhancing the immune response of head and neck cancer patients

“…Immunotherapy using cytokines started in the 1980s and continues to be evaluated for the treatment of cancer; it has met with only limited success in HNSCC. IL‐2 and interferon (IFN)‐α were the first cytokines tested in HNSCC 12,13,17,19,20,27–35 . A preliminary trial of nonrecombinant IFN‐α in patients with HNSCC was performed by Vlock and colleagues, 27 which demonstrated tolerable toxicity and potential anti‐tumor activity.…”

“…Clinical and pathologic findings indicated that tumor regression was observed in several cases and was mediated by activated lymphocytes accumulating at the tumor site 33,34 . Combinations of cytokines with chemotherapy have also been evaluated in HNSCC, 35 but there has been no benefit identified from the addition of IL‐2 or IFN‐α to standard chemotherapy.…”

Immunotherapy for Head and Neck Cancer Patients: Shifting the Balance

“…IL-10 can work as an immune suppressor, whereas cytokines such as IL-2 and IL-12 promote T cell growth. The cytokine investigated the most for immunotherapy is IL-2; several trials have been performed for HNSCC [116][117][118][119][120][121][122]. Given in high doses, IL-2 can be toxic [119].…”

“…Furthermore, it is a concern that high levels of IL-2 induce Treg expansion, resulting in the suppression of surrounding lymphocytes. Lower doses of IL-2 have been used and tested in a Phase III trial [120]. In this trial, patients were either given chemotherapy alone or in combination with low-dose IL-2.…”