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The aims of the present open, randomized, single-blind (patient), single institution, phase II study were: i) to compare the therapeutic effectiveness and toxicity of two dosages and schedules of ifosfamide (IFO) in combination with cisplatin (CDDP) mainly in the neo-adjuvant setting of patients (pts) with locally advanced (stage III-IV) head and neck squamous cell cancer (HNSCC) (primary endpoint); ii) to assess the quality of life (QL) of pts included in the study before and after treatment (secondary endpoint). From July 1996 to June 1997, 28 pts, all males (mean age 56.79 years, range 37-72), hospitalized in the Department of Medical Oncology, University of Cagliari, were enrolled in the study. Twenty pts (M/F 20/0, mean age 53.6, range 37-71 years; stage III 1 pt, stage IV 19 pts) were evaluable for response and all 28 pts enrolled were evaluable for toxicity. Arm A: IFO 2.2 g/m2 i.v. as a 4 h infusion on days 1-5, Mesna 600 mg i.v. as push injection at 0 h, 4 h, 8 h on days 1-5, CDDP 20 mg i.v. as a 60 min infusion on days 1-5. The regimen was repeated every 28 days for 2 cycles. Fifteen pts (11 of whom were evaluable) were enrolled in this Arm. Arm B: IFO 1.5 g/m2 i.v. as a 4 h infusion on days 1-5, Mesna 600 mg i.v. as push injection at 0 h, 4 h, 8 h on days 1-5, CDDP 20 mg i.v. as a 60 min infusion on days 1-5. The regimen was repeated every 28 days for 3 cycles. Thirteen pts (9 of whom were evaluable) were enrolled in this Arm. The two Arms were well-balanced for sex, age, site of primary, ECOG PS and clinical stage. After completion of 2 (Arm A) or 3 (Arm B) cycles of chemotherapy, the pts were assessed for response. All evaluable pts received treatment as planned. Six pts (54.5%) of Arm A and 4 pts (44.5%) of Arm B had partial response (PR) with an overall response rate (ORR) of 54.5% and 44.5%, respectively: it is worth noting that all (100%) pts who had PR in Arm B achieved a high-grade PR, i.e. >/=70%, whereas only one pt (16.7%) who had PR in Arm A achieved a high-grade PR. Three pts (27.3%) in Arm A and 2 pts (22.2%) in Arm B had stable disease (SD); 2 pts (18.2%) in Arm A and 3 pts (33.3%) in Arm B had progressive disease (PD). The actual dose intensity was over 80% of the projected dose intensity for both drugs and for both Arms. Over a total of 59 cycles administered, the total number of episodes of toxicity was 24 for Arm A and 17 for Arm B. Three pts out of 28 evaluable for toxicity (10.8%) died for Grade 5 hematological toxicity: all pts were included in Arm A. In Arm A, 2 pts (13.3%) experienced hematological Grade 3 toxicity and 2 pts (13.3%) hematological Grade 4 toxicity. In Arm B no pt experienced Grade 3-4 hematological toxicity. No Grade 3-4 toxicity of any other type was found in either Arm. The QL evaluation, using the Cella's FACT-G scale supplemented with disease-specific scale (FACT-H&N scale), did not show significant beneficial effect of neo-adjuvant chemotherapy treatment.

We designed an open, non-randomized, phase II clinical study to assess as the first endpoint the feasibility of sparing surgery and of preserving organ/function by using neoadjuvant chemotherapy (NAC) laryngeal cancer patients, and, as the second endpoint, the clinical response to this treatment approach and its duration. 32 patients with primary laryngeal cancer (stage III-IV) were enrolled in the study and were assigned to either the classical Al-Sarrafs regimen (20 patients) or to a regimen consisting of cisplatin 80 mg/m(2) i.v. on day 1, 5-FU 600 mg/m(2) on days 2-5 and vinorelbine 20 mg/m(2) on days 2 and 8 (12 patients). The patients were divided into 2 groups: A) those requiring total laryngectomy (TL) and B) those not requiring TL, i.e. patients eligible for conservative for conservative surgery. The 32 patients were all evaluable for response to NAC and 31 were evaluable for The complete remission rate was 50% (16/32) and the partial remission rate was 46.9% (15/32) with an overall response rate of 96.9%. The median follow-up duration was 20.2 months. Overall, 23 patients required TL (group A) and 8 patients a conservative laryngectomy (group B). 7/23 (30.5%) patients of group A did not undergo surgery (score 4) and 6/23 (26%) achieved a partial larynx preservation (3/23 score 3, 1/23 score 2, 2/23 score 1), while 10/23 (43.5%) received the previously planned TL (score 0). 5/8 (62.5%) patients of group B did not undergo surgery, whereas 3/8 (37.5%) received the previously planned surgery (score 0). Therefore, 12/31 patients (38.7%) completely avoided surgery and 6/31 (19.4%) achieved a reduction in the extent of planned surgical resection, that is 18/31 patients (58.1%) achieved a reduction in the extent of previously planned surgery attributable to NAG. Moreover, 3/31 patients underwent the previously planned conservative surgery consisting of H-SGL/HG. Altogether 21/31 (67.7%) patients preserved function. The most relevant contributions offered by our study are represented by i) a scale aimed at measuring as precisely as possible the reduction of surgical resection made possible by NAC compared to surgery planned before NAC and ii) by an attempt to support the results with an assessment of patients treatment outcome. Although the scale provided by us is an arbitrary one, it must be emphasized that our goal was to address the issue of quality of life in cancer patients by a more precise quantification of organ/function preservation.

We designed an open, non-randomized clinical study to assess as the first endpoint the feasibility of sparing surgery and of preserving organ/function by using neo-adjuvant chemotherapy (NAG) in oral cavity and oropharynx cancer patients, and, as the second endpoint, the clinical response to this treatment approach and its duration. Moreover, an attempt was made to scale the extent of surgery by means of an Arbitrary Scale assigning different percentages to the different extents of surgical resection. Twenty-five patients with primary oral cavity and oropharynx cancer (stage III-TV) were enrolled in the study and were assigned to either the classical Al-Sarrafs regimen (1) (n=15) or to a regimen (2) consisting of cisplatin 80 mg/m(2) i.v. on day 1, 5-FU 600 mg/m(2) on days 2-5 and vinorelbine 20 mg/m(2) on days 2 and 8 (n=10). The 25 patients were all evaluable for response to NAC and 20 of them were evaluable for organ preservation. The overall response (OR) rate was 86.6% (13/15 patients) for regimen 1 (cisplatin + 5-FU) and 80% (8/10 patients) for regimen 2 (cisplatin + 5-FU + vinorelbine). The median follow-up duration was 20.6 months. 5/20 (25%) patients completely avoided surgery, 5/20 (25%) patients had a reduced extent of surgical resection, while: 10/20 (50%) patients received the previously planned surgical resection. Altogether, 10/20 (50%) patients treated with NAC either avoided or achieved a reduction in the previously planned surgical resection. Moreover, organ function was evaluated to support the assessment of treatment outcome in our patients. For this purpose we selected the Performance Status Scale for Head and Neck Cancer Patients: as expected, no significant impairment was detected in the area of comprehensibility of speech, but we were rather surprised that no significant impairment was found in the two areas of eating in public and normalcy of diet. NAG-associated toxicity was moderate and similar in the two chemotherapy regimens. The most relevant contributions offered by our study are represented by i) a Scale aimed at measuring as precisely as possible the reduction of surgical resection made possible by NAC compared to surgery planned before NAC and ii) an attempt to support the results with an assessment of treatment outcome.