Unresectable Squamous Cell Carcinoma Research Articles

Pharmacodynamic study of nimotuzumab, an anti-epidermal growth factor receptor (EGFR) monoclonal antibody (MAb), in patients with unresectable squamous cell carcinoma of the head and neck (SCCHN): A SENDO Foundation study

6070 Background: Nimotuzumab (N) is a humanized MAb to EGFR that has shown evidence of efficacy in patients (pts) with advanced solid tumors, notably without provoking skin rash. Although lack of rash might be a therapeutic advantage, evidence of biological activity of N is needed. To this end, a PD study was performed. Methods: Ten pts with advanced SCCHN, unsuitable for chemo-radiotherapy, were enrolled in a single center phase Ib clinical trial. Pts received 8 weekly infusions of N at 2 dose levels: 200mg and 400mg. The first N infusion was administered 1 week before starting radiation while remaining doses were delivered concomitantly with irradiation. Paired biopsies were taken from skin and primary tumors, before (pre-therapy) and 1 week (on-single agent therapy) after first infusion. A PD study by immunohistochemistry was conducted to assay the effects of N on EGFR—total and phosphorylated (p)—and its signaling pathways ERK and AKT (total and p) as well as proliferation (Ki67). Results: N was well tolerated and there was no evidence of skin rash in any of the treated pts. Objective response was achieved in 80% of pts (2 CR, 6 PR). Median survival time was 7.2 months. PD showed inhibition of p- EGFR in both skin and tumor (Wilcoxon test, p=0.042 skin, p=0.034 tumor). Inhibition of downstream pathways was suggested by a trend in the decrease of p-ERK (p=0.091) and a significant reduction in proliferation (p=0.012). Upregulation of p-AKT was observed in tumor (p=0.043) but not in skin, similarly to what has been reported for other anti-EGFR agents. Characteristic lymphocytic infiltrates, folliculitis or perifolliculitis induced by other EGFR inhibitors were not observed. No associations were found between doses or response and PD effects. Conclusions: These data show that after a short period of exposure, N as a single agent inhibited EGFR phosphorylation and this was accompanied by a trend towards molecular downstream effects consistent with the expected biological effects of EGFR targeting. The absence of inflammatory skin reaction might be linked to the lack of skin toxicity by N. The response rate observed with N and radiation is promising. No significant financial relationships to disclose.

Cetuximab as first-line monotherapy in patients with unresectable squamous cell carcinoma of the skin: Preliminary results of a phase II multicenter study

9042 Background: Patients (pts) with advanced squamous cell carcinoma of the skin (SCCS) have a poor prognosis. Cetuximab (C), an IGg1 monoclonal antiboby that blocks the epidermal growth factor re...

Concomitant Chemoradiotherapy With Mitomycin C and Cisplatin in Advanced Unresectable Carcinoma of the Head and Neck: Phase I–II Clinical Study

To evaluate the toxicity and efficacy of concomitant chemoradiotherapy with mitomycin C and cisplatin in the treatment of advanced unresectable squamous cell carcinoma of the head and neck. Treatment consisted of conventional radiotherapy (70 Gy in 35 fractions), mitomycin C 15 mg/m(2) IV, applied after the delivery of 10 Gy, and cisplatin at an initial dose of 10 mg/m(2)/d IV, applied during the last 10 fractions of irradiation ("chemoboost"). The cisplatin dose was escalated with respect to the toxic side effects by 2 mg/m(2)/d up to the maximum tolerated dose (MTD) or at the most 14 mg/m(2)/d (Phase I study), which was tested in the subsequent Phase II study. All 36 patients had Stage T4 and/or N3 disease, and the majority had oropharyngeal (50%) or hypopharyngeal (39%) primary tumors. Six patients were treated at each of the three cisplatin dose levels tested (Phase I study). Dose-limiting toxicity was not reached even at 14 mg/m(2)/d of cisplatin, which was determined as the MTD and tested in an additional 18 patients (Phase II study). After a median follow-up time of 48 months, 4-year locoregional control, failure-free, and overall survival rates were 30%, 14%, and 20%, respectively. In 24 patients treated at the cisplatin dose level of 14 mg/m(2)/d, the corresponding rates were 40%, 20%, and 22%, respectively. Concomitant chemoradiotherapy with mitomycin C and cisplatin "chemoboost" at 14 mg/m(2)/d is feasible, with encouraging survival results if the extremely poor disease profile of the treated patients is considered.

Feasibility Study of Single Agent Cisplatin and Concurrent Radiotherapy in Japanese Patients with Squamous Cell Carcinoma of the Head and Neck: Preliminary Results

Concurrent chemoradiotherapy with the single agent cisplatin (CDDP + RT) has been recognized worldwide as the standard treatment for unresectable locally advanced SCCHN. The objective of this study was to clarify the feasibility of CDDP + RT in Japanese patients. Patients and methods Patients with unresectable squamous cell carcinoma of the head and neck were given single daily fractionated radiation (70 Gy at 2 Gy/day) and chemotherapy consisting of a 2 h infusion of CDDP 100 mg/m(2) on days 1, 22 and 43. The primary endpoint was the rate of completion of CDDP + RT. Between November 2005 and January 2007, 20 patients were enrolled, 19 males and one female with a median age of 61.5 years (range 50-74). One patient had recurrent unresectable disease after surgery and the remaining 19 had stage IV disease. No grade 4 hematologic toxicities were observed. The incidence of grade 3 mucositis was 55% and no treatment-related death occurred. Full-dose irradiation was performed in all patients, with a median duration of radiotherapy of 50 days (range 48-54). Although all patients received the first two administrations of CDDP, the third dose was administed in 17 patients (85%). The rate of completion of CDDP + RT was 85% and the dose intensity of CDDP was 28.9 mg/m(2)/week (relative dose intensity 89%). Overall complete response rate was 50% and the rate of primary complete response was 90%. Concurrent chemoradiation therapy with the standard dose of CDDP is feasible in Japanese patients. Treatment modification based on racial differences is not necessary.

Final report of RTOG 9610, a multi‐institutional trial of reirradiation and chemotherapy for unresectable recurrent squamous cell carcinoma of the head and neck

Our objectives were to determine the incidence of acute and late toxicities and to estimate the 2-year overall survival for patients treated with reirradiation and chemotherapy for unresectable squamous cell carcinoma of the head and neck (SCCHN). Patients with recurrent squamous cell carcinoma or a second primary arising in a previously irradiated field were eligible. Four weekly cycles of 5-fluorouracil 300 mg/m2 IV bolus and hydroxyurea 1.5 g by mouth were used with 60 Gy at 1.5 Gy twice-daily fractions. Toxicity was scored according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) criteria. Seventy-nine of the 86 patients enrolled were analyzable. The worst acute toxicity was grade 4 in 17.7% and grade 5 in 7.6%. Grade 3 and 4 late toxicities were found in 19.4% and 3.0%, respectively. The estimated cumulative incidence of grade 3 to 4 late effects occurring at >1 year was 9.4% (95% confidence interval [CI]: 0, 19.7) at 2 and 5 years. The 2- and 5-year cumulative incidence for grade 4 toxicity was 3.1% (95% CI: 0, 9.3). The estimated 2- and 5-year survival rates were 15.2% (95% CI: 7.3, 23.1) and 3.8% (95% CI: 0.8, 8.0), respectively. Patients who entered the study at >1 year from initial radiotherapy (RT) had better survival than did those who were <1 year from prior RT (median survival, 9.8 months vs 5.8 months; p = .036). No correlation was detected between dose received and overall survival. Three patients were alive at 5 years. This is the first prospective multi-institutional trial testing reirradiation plus chemotherapy for recurrent or second SCCHN. The approach is feasible with acceptable acute and late effects. The results serve as a benchmark for ongoing RTOG trials.

Cost-effectiveness analysis of the EORTC 24971 (TAX 323) trial comparing docetaxel plus cisplatin and 5-fluorouracil versus standard treatment (cisplatin and 5-fluorouracil) as induction chemotherapy followed by radiation therapy in locally advanced unresectable squamous cell carcinoma of the head and neck (SCCHN)

6090 Background: The phase III EORTC 24971 clinical trial (TAX 323) showed that induction chemotherapy followed by radiation therapy increases time to progression and improves outcomes in unresectable SCCHN patients. [Remenar et al. ASCO 2006; Abs 5516] Induction chemotherapy with cisplatin/5-FU (PF) is a standard regimen for patients with locally advanced SCCHN. The economic impact of adding docetaxel to cisplatin/5-FU (TPF) in this setting was assessed using a Markov state-transition model. Methods: The Markov model includes four health states (based on WHO criteria for measuring objective response): stable, response, progression, and death. Efficacy data from the TAX 323 clinical trial were used to derive transition probabilities between the health states. Adverse event rates were also derived from TAX 323. Data for resource utilization and costs for the UK were derived from the literature and from an advisory board of clinicians. In order to calculate quality adjusted life years (QALYs), utilities were derived by mapping the global score on the Health Related Quality of Life Questionnaire Core-30 (QLQ-C30) to the EQ-5D. Results: Patients survived longer in the TPF arm versus PF (2.5 vs. 2.0 years). Total costs for TPF and PF were £31,203 and £26,944, respectively. The incremental discounted cost per QALY gained for TPF versus PF was £9,859/QALY, which is below the £20,000 cost-effectiveness threshold suggested by NICE as a guide to the acceptability of a technology. Conclusion: Docetaxel, when given as induction chemotherapy in combination with cisplatin/5-FU, is cost-effective compared with PF in locally advanced unresectable SCCHN patients. Treating SCCHN patients with TPF followed by radiation represents good value for money based on the results of the analysis. No significant financial relationships to disclose.

Feasibility study of capecitabine (cap) and cisplatin (cis) with radiation therapy (RT) in the management of patients with locally advanced unresectable squamous cell carcinoma of the head and neck (HNSCC)

16520 Background: Concurrent chemoradiation has become the standard of care for locally advanced unresectable HNSCC. The most commonly used chemotherapy is cis and 5-fluorouracil (5-FU). We evaluated the feasibility of using cap and cis during RT in this population. Cap is an oral pro-drug of 5-FU that can be given daily with RT in order to enhance the activity of RT. Methods: Between Oct, 2003 and Sept, 2005, 12 male patients aged 46–83 were treated at the VA Medical Center. Patients received cis 100 mg/m2 on days 1 and 29 and cap 450 mg/m2 bid (2 hours prior to RT and 12 hours later) for 5 days of each week concurrent with RT to a total dose of 70 Gy in 35 fractions over 7 weeks. Primary endpoint of the study was toxicity. Results: All 12 patients were able to complete therapy. Treatment delays and/or dose modifications were needed in 7 patients. Treatment related toxicities included 6 patients with grade 3 mucositis and 5 patients with grade 3 dysphagia. Other grade 3 toxicities included 3 patients with dehydration and 1 patient each with leucopenia, constipation, nausea and vomiting, and odynophagia. Percutaneous gastrostomy (PEG) tubes were required in 5 patients. Complete response to chemoradiation was seen in 9 patients, 2 patients obtained partial response, and 1 patient progressed. Median progression free and overall survivals have not been reached with a median follow-up of 21 months. Conclusions: Cis and cap administered concurrently with RT has manageable toxicities and is active in patients with locally advanced unresectable HNSCC. No significant financial relationships to disclose.

INGN 201

INGN 201

199 POSTER Efficacy evaluation of the humanized anti-EGFR MAb h-R3 (nimotuzumab) in combination with radiotherapy in the treatment of patients with unresectable squamous cell carcinomas of the head and neck

Receptor activator of NF-κB ligand (RANKL) is a type II transmembrane protein found on osteoblasts which functions as a major determinant of osteoclast differentiation and activation. RANKL mediates bone homeostasis through binding to the cognate ligand on osteoclasts, RANK, and a soluble decoy receptor, osteoprotegerin (OPG). We designed a construct encoding the extracellular domain of human RANKL that conformed to reports of native processing. To encourage folding and posttranslational modification of a normally membrane-inserted moiety, we expressed the RANKL truncate as a secreted protein using the signal sequence from OPG in a Trichoplusia ni cell line using a baculovirus expression vector. RANKL was purified by a three-step process including an OPG-Fc affinity column. SDS–PAGE and mass spectral analysis indicated that the protein was >99% pure and glycosylated. Circular dichroism spectra revealed that the protein exhibited structural elements similar to tumor necrosis factor-α. By BIAcore analysis, RANKL bound to OPG with an affinity of 6.7 nM. Sedimentation equilibrium analytical ultracentrifugation analyses established that our protein existed as a trimer. We conclude that our expressed human RANKL truncate is folded, is functional, and exhibits self-association consistent with other family members.

Impact on quality of life (QoL) of the addition of docetaxel (T) to neoadjuvant cisplatin plus 5-fluorouracil treatment in patients with locally advanced unresectable squamous cell carcinoma of the head and neck (SCCHN): EORTC study 24971

5522 Background: The EORTC 24971 trial compared the efficacy and safety of two neoadjuvant regimens in the treatment of stage III or IV, M0 SCCHN. Eligible patients (pts) with primary tumor sites in the oral cavity, oropharynx, hypopharynx, and larynx and WHO performance status (PS) ≤1) were randomized to 2–4 cycles of cisplatin (P) 100 mg/m2 day 1, followed by a continuous infusion of 5-fluorouracil (F) 1000 mg/m2/day from days 1- 5 (PF), or T 75 mg/m2 + P 75 mg/m2 day 1 then F 750 mg/m2/day from days 1 - 5 (TPF), followed by locoregional radiation therapy (RT). The impact of the two regimens on QoL was a secondary endpoint. Methods: QoL was assessed at baseline, at cycles 2 and 4, and 6 and 9 months after RT using the EORTC QLQ-C30 questionnaire to obtain the Global Health Status/Quality of Life (GHS/QoL) score, and the Head and Neck Performance Status Scale (PSS-HN) to assesses the normality of diet, eating in public, and understandability of speech on a scale of 0 to 100. The EORTC QLQ-HN35 questionnaire was also administered at those time-points. Results: 358 pts were randomized to PF (181 pts) or TPF (177 pts). Baseline (BL) characteristics of the pts were well balanced between groups. TPF was superior to PF in terms of response rate, progression-free survival (primary endpoint), overall survival, and tolerability. Compliance with the QLQ-C30 questionnaire was good ranging from 96% at BL to 41% at 9 months post RT, and was similar between the treatment arms. GHS/QoL scores were comparable at BL between the two arms (p = 0.54) and improved in both arms on starting treatment. Over time this score remained stable with TPF, but decreased after RT with PF (treatment-time interaction: p = 0.009). Evolution of the PSS-H&amp;N score was better on TPF (normality of diet p= 0.0064; eating in public p = 0.0004; understandability of speech p = 0.0003). Moreover, TPF was associated with a 30% reduction in the risk of WHO PS deterioration (p = 0.0158) Conclusions: The use of docetaxel in neoadjuvant treatment of SCCHN improves efficacy without deleterious effects on QoL and functional outcomes. [Table: see text]

A randomized phase III multicenter trial of neoadjuvant docetaxel plus cisplatin and 5-fluorouracil (TPF) versus neoadjuvant PF in patients with locally advanced unresectable squamous cell carcinoma of the head and neck (SCCHN). Final analysis of EORTC 24971

5516 Background: So far, the Wayne State regimen combining 100 mg/m2 cisplatin on day 1 and 1000 mg/m2/d continuous infusion 5-fluorouracil over 5 days (PF), is the gold standard in advanced SCCHN. Improvement of PF induction chemotherapy by adding a taxane has been suggested from phase II studies and 2 randomized phase III trials. We now report the final analysis of EORTC 24971. Methods: Eligible were patients (pts) with unresectable stage III/IV SCCHN (no distant metastases), 18 to 70 yrs of age, PS≤1, and adequate hematologic, renal and hepatic function. Pts were stratified by primary disease site (oral cavity, oropharynx, hypopharynx, larynx) and treatment center and randomized to PF (as above) or TPF (T 75 mg/m2/1h, P 75 mg/m2/1h, both d1, F 750 mg/m2/d, d1–5) q 3 wks, for 4 cycles unless progression (PD) or unacceptable toxicity, or refusal. Thereafter (interval 4–7 wks), all pts not in PD received radiotherapy (RT: conventional [66–70 Gy], accelerated [max. 70 Gy] / hyperfractionated [max. 74 Gy]). Surgery was allowed before RT (neck) or 3 months after RT (primary, neck). Primary endpoint was progression-free survival (PFS), and 348 pts and 260 events were needed to detect a 50% increase in median PFS (10 vs 15 mo) with 85% power. Results: Between April 1999 and March 2002, 358 pts were accrued (181 PF, 177 TPF). At a median follow-up (FUP) of 32 mo, PFS was significantly improved with TPF (HR 0.72, p = 0.0071; median 8.2 vs 11.0 mo). A 51 mo median FUP showed an overall survival (OS) benefit with TPF (HR 0.71, p = 0.0052; median 14.2 vs 18.6 mo). Estimated 3-yr survival rates are 23.9% (95% CI: 17.9%;30.5%) for PF and 36.5% (29.3%;43.6%) for TPF. Response rate also favored TPF (53.6% vs 67.8%, p = 0.006). There was more severe (G3+4) leucopenia (41.6% vs 22.9%) and neutropenia (76.9% vs 52.5%) with TPF, and more severe thrombocytopenia with PF (17.9% vs 5.2%). Severe alopecia occured more with TPF (55.5% vs 11.7%); hearing loss (2.8% vs 0%) and toxic death (7.8% vs 3.7%) more with PF. Conclusions: TPF (→ RT) is superior to PF (→ RT) for PFS, OS (including long-term), response rate, and is better tolerated. [Table: see text]

Induction chemotherapy followed by concurrent chemoradiation in advanced squamous cell carcinoma of the head and neck: Final results from a phase II study with docetaxel, cisplatin and 5-fluorouracil with a four-year follow-up

Encouraging results have recently been reported in patients (pts) with locally advanced unresectable squamous cell carcinoma of the head and neck (SCCHN) when induction chemotherapy (IC) is used and followed by radiotherapy (RT). The present study assessed the therapeutic response of an aggressive regimen consisting of docetaxel (TXT), cisplatin (CDDP) and 5-fluorouracil (5-Fu) as IC and concurrent with RT in pts with locally advanced (stages III and IV) SCCHN. 42 pts (35 male and 7 female) with a mean age of 58 years suffering from stages III and IV (Mo) SCCHN were included to this organ preservation phase II clinical trial. The site of the primary tumors was the anterior mouth in 9 pts, base of tongue and oropharynx in 12, middle third of the face in 8 and larynx in 13. The performance status of the pts was 0-1 according to WHO and above 80% according to Karnofsky classification. IC consisted of TXT (40 mg/m2), CDDP (40 mg/m2) and 5-Fu (350 mg/m2) every two weeks (wks) for a total of four courses and repeated, coupled with RT (66-68 cGys total dose fractionated at 200 Gy per day, 5 days a week), for up to seven wks. In total, pts received eight courses of chemotherapy (CT) at the end of RT treatment. Pts were evaluated at the end of IC, after RT and every six wks thereafter. 41 pts were eligible for evaluation after IC (one died from myocardial infarction) and 39 after completion of treatment (two died during RT). Statistical multivariate analysis was performed using SPSS (11) package. Complications from IC and RT were evaluated according to WHO criteria and included mucositis Grade (Gr) IV in 10% of the pts, Gr III in 50%, Gr II in 20%. Anemia presented in 40% of the pts with Gr II, 40% with Gr I, neutropenia 17% with Gr IV, 20% with Gr III, 30% with Gr II, thrombocytopenia 3% with Gr III, 10% with Gr I and xerostomia up to Gr II in 70% of the pts. The response rate (RR) after IC was complete response (CR) for 10 pts (24.4%), partial response (PR) for 22 (53.7%) and no response (NR) for 9 (21.9%). At the end of the treatment the RR in the intention-to-treat population were CR for 25 pts (64.1%), and PR for 14 (35.9%). Follow up ranges from 18 to 56 months (mts). 14 pts died during follow-up time. The mean survival time is 41 mts and the median 40. 2 pts with CR developed local recurrence and two distant metastases, whereas all pts with PR developed progressive disease (PD) and all but two are dead from disease. It is evident from this phase II study that TXT-CDDP-5Fu based IC followed by the same regimen coupled with RT improves local control. Pts that showed CR after IC continued to maintain disease status during RT (P-value=0.0181). In pts with SD concurrent RT did not alter dramatically disease outcome. Patients who showed complete response after both IC and RT presented a four-year survival rate of 74% compared to a 30% to partial responders (P-value=0.0001). Results are encouraging and further study of the toxicity and follow-up is needed to validate treatment effectiveness.

Radiation Therapy With 5-fluorouracil in Head and Neck Cancer.

5-Fluorouracil (5-FU) alone or combined with other drugs, most frequently cisplatin, has been used concurrently or as induction or adjuvant therapy with radiotherapy with or without surgery in the treatment of head and neck cancer. Improved local-regional control and disease-free survival or overall survival have been shown in several randomized trials using a concurrent approach. However, acute mucositis is usually increased with simultaneous 5-FU and radiation administration, especially when other drugs are used in addition to 5-FU. Alternating radiotherapy with 5-FU and cisplatin was shown to improve the local-regional relapse-free, progression-free, and overall survival of unresectable squamous cell carcinoma of the head and neck compared with radiotherapy alone in one randomized trial. Further evaluation of the alternating chemotherapy and radiotherapy approach is needed, however, before one can accept this as a standard of practice. Induction chemotherapy with 5-FU infusion and cisplatin followed by definitive radiotherapy in the chemotherapy responders in an alternative treatment option for patients with locally advanced resectable squamous cell carcinoma of the larynx or hypopharynx who wish to preserve organ function. Induction or adjuvant chemotherapy with 5-FU infusion and cisplatin may also decrease or delay the occurrence of distant metastasis. Induction chemotherapy, however, has not been shown to improve local-regional control or overall survival. Further clinical trials combining 5-FU and its biochemical modulators using innovative radiation and drug dose schedules and other treatment modifiers are needed to improve the therapeutic ratio.

1030 POSTER Capecitabine and cisplatin combination chemotherapy as salvage therapy for recurrent unresectable or metastatic squamous cell carcinoma of the head and neck

1030 POSTER Capecitabine and cisplatin combination chemotherapy as salvage therapy for recurrent unresectable or metastatic squamous cell carcinoma of the head and neck

Toxicity and outcome analysis of patients with recurrent head and neck cancer treated with hyperfractionated split‐course reirradiation and concurrent cisplatin and paclitaxel chemotherapy from two prospective phase I and II studies

Patients with local recurrences or new head and neck primary tumors in previously irradiated tissues have few options for salvage treatment. One option for select patients is to undergo reirradiation with concurrent chemotherapy. The purpose of this study is to report the initial clinical results of the Fox Chase phase I and II prospective reirradiation and chemotherapy studies. Between July 1996 and January 2002, 38 patients with locally recurrent unresectable squamous cell carcinoma of the head and neck were treated with concurrent chemotherapy and reirradiation on two prospective trials. All patients had received prior radiation therapy to the head and neck region (median dose, 64.2 Gy). Patients received cisplatin and paclitaxel along with hyperfractionated external beam radiation therapy to the site of recurrence. The median follow-up was 10 months. The median survival was 12.4 months, with actuarial rates of overall survival of 50% and 35% at 1 and 2 years, respectively. During follow-up, 63% of patients experienced local progression of disease, all in the irradiated field. Actuarial progression-free survival at 1 year was 33%, with a median time to progression of 7.3 months. Acute grade 3 to 4 toxicity included neutropenia, nausea, emesis, and mucositis. Hyperfractionated split-course reirradiation and concurrent cisplatin and paclitaxel chemotherapy demonstrates durable locoregional control in select patients, although late toxicity may occasionally be significant. Only sites of disease recurrence need to be covered in the reirradiation fields.

PD.194 Radiation (RT) concurrent with gemcitabine(GEM) for unresectable squamous cell carcinoma in the head and neck (SCCHN). A phase II trial

PD.194 Radiation (RT) concurrent with gemcitabine(GEM) for unresectable squamous cell carcinoma in the head and neck (SCCHN). A phase II trial

Phase II trial of cisplatin and capecitabine in patients with squamous cell carcinoma of the head and neck, and correlative study of angiogenic factors

The combination of cisplatin and capecitabine was evaluated in patients with recurrent or unresectable squamous cell carcinoma of the head and neck (HNSCC), and outcome parameters were correlated with the expression of thymidine phosphorylase (TP), thymidilate syntetase (TS), vascular endothelial growth factor receptor (VEGFR) 1–3, and microvessel density (MVD). Patients with recurrent or unresectable HNSCC were eligible if they had received prior neoadjuvant chemotherapy, concurrent chemo-radiotherapy, or no prior systemic therapy. Patients received cisplatin (75 mg m−2 day 1), and capecitabine (2000 mg m−2 day 1–14) every 3 weeks. A total of 41 patients received 194 cycles. In all, 16 complete responses (39%) and 12 partial responses (29%) were documented, for an overall response rate of 68% (95% CI, 53–80%). Grade 3–4 uncomplicated neutropenia was documented in five subjects. Asthenia, anorexia, hand–foot syndrome, and constipation were the most frequent nonhaematologic events. Median progression-free and overall survival were 6.4 and 12.6 months. Cytoplasmic TP expression was more prevalent in patients with a laryngeal location vs other, and in patients with a recurrence vs primary disease. Microvessel density count was higher in patients with recurrent vs primary disease. The combination of cisplatin and capecitabine is effective in recurrent or unresectable HNSCC, and shows a manageable toxicity.

Simultaneous radio- and chemotherapy for squamous cell carcinoma of the head and neck in daily clinical practice: 5 years experience in a University Hospital

Several randomized studies and meta-analyses have shown that simultaneous radio- and chemotherapy prolongs survival in patients with unresectable squamous cell carcinoma of the head and neck as compared with conventional radiotherapy. We assessed the feasibility and effectiveness of simultaneous radiotherapy (35 x 2 Gy) and chemotherapy [cisplatinum 100 mg/m(2) or carboplatin (AUC 6) on days 1, 22 and 43] in daily clinical practice in a cohort of 87 patients treated at our institute between 1998 and 2002. Eighty patients completed radiotherapy according to schedule. Eighty patients received two courses of chemotherapy and 50 patients three courses. Nephrotoxity, bone marrow suppression and ototoxicity were the most frequent side-effects. Median weight loss was 8.5%. Median survival was 15 months and 44% of the patients were alive at 2 years. Patients receiving three courses of chemotherapy had a better survival than patients receiving two or less courses. Treatment with simultaneous radio- and chemotherapy for advanced head and neck cancer is a demanding, but feasible treatment in daily clinical practice. Survival seems to be comparable with the results achieved in patients selected for clinical trials.

Long-term survival and functional quality of life assessments in patients with locally advanced unresectable squamous cell carcinomas of the head and neck treated with concurrent chemoradiation

Concurrent chemotherapy and radiation has been shown to be effective treatment for unresectable squamous cell carcinomas of the head and neck (SCCHN). While initial data has been encouraging, few studies have reported 5-year survival in conjunction with patient-assessed functional quality of life (QOL) outcomes. This report details the long-term survival and laryngeal/pharyngeal functional outcome of a phase II trial evaluating the combination of weekly carboplatin (CBDCA), paclitaxel, and daily radiation for patients with locally advanced unresectable disease. From 1993–1998, 62 patients with Stage III-IV SCCHN were prospectively treated with RT to 70.2 Gy at 1.8 Gy/fraction/day with weekly chemotherapy consisting of paclitaxel (45 mg/m(2)/wk) and carboplatin (100 mg/m(2)/wk). All patients presented with locally advanced disease (93% Stage IV); 77% had T4 disease and 21% had T3 disease. Fifty-eight percent had N2b-N3 disease. Sixty patients were evaluated for response and survival with a mean follow-up of 52 months (range 2–119). In March 2004, long-term functional and symptom-related quality of life analysis was performed in surviving patients using the Quality of Life-Radiation Therapy Instrument HeadsNeck Module (QOL-RTI/H&N). This questionnaire assesses pain, appearance, speech, chewing and swallowing, mucous and saliva, taste, and cough on a 0–10 Likert type scale, with a QOL score (QS) of 10 representing the highest perceived toxicity. Ninety-eight percent of patients completed the prescribed therapy. A clinical complete response (CR) at the primary site was obtained in 82%, with a total (primary site and neck) CR rate of 75%. Local-control for the entire cohort at 1 year, 3 years, and 5 years was 76.6%, 66.9% and 62.1% respectively. Overall survival (OS) at 1 year, 3 years, and 5 years was 77.1%, 50.7%, and 38.9% respectively, with a median OS of 37.3 months. Nineteen patients were eligible for QOL analysis, with a mean survival of 75.7 months. The most significant decrement in QOL for surviving patients included a decrease in chewing function, with all cases due to teeth extraction (mean QS 5.91), difficulty swallowing solid foods (mean QS 5.73), thickened saliva (mean QS 5.64), decreased amount of saliva (mean QS 4.82), and decreased taste sensation (mean QS 4.45). Factors that had an intermediate effect on long-term QOL included frequent or severe cough (mean QS 2.00), eating in public (mean QS 2.18), increased mucous production (mean QS 2.27), and difficulty speaking (mean QS 2.82). Long-term QOL factors which were least affected by concurrent chemoradiation include (in descending order): pain in the mouth (mean QS 0.73), cosmesis of face or neck (mean QS 1.27), pain in the throat (mean QS 1.73), swallowing liquids (mean QS 1.82), and eating regular foods (mean QS 1.91). The long term survival analysis of this phase II institutional study supports our contention that weekly carboplatin and paclitaxel with definitive daily external beam radiation therapy provides excellent local control (62%) and improved survival (39%), in patients presenting with locally advanced unresectable SCCHN. In addition, this QOL assessment reveals that surviving patients were most significantly impacted by the long-term effects of xerostomia, and had minimal chronic toxicities related to pain and cosmesis

Long-term survival and functional quality of life assessments in patients with locally advanced unresectable squamous cell carcinomas of the head and neck treated with concurrent chemoradiation

Concurrent chemotherapy and radiation has been shown to be effective treatment for unresectable squamous cell carcinomas of the head and neck (SCCHN). While initial data has been encouraging, few studies have reported 5-year survival in conjunction with patient-assessed functional quality of life (QOL) outcomes. This report details the long-term survival and laryngeal/pharyngeal functional outcome of a phase II trial evaluating the combination of weekly carboplatin (CBDCA), paclitaxel, and daily radiation for patients with locally advanced unresectable disease.