Abraxane in Combination With Carboplatin, Erbitux and IMRT for Locally Advanced Squamous Cancer of the Head and Neck

Disease-free survival (DFS) is defined as the time from registration to the earlier of disease recurrence or death from any cause. Patients alive without a recurrence are censored at the date of last disease evaluation. 2-year disease-free survival is the probability of patients remaining alive and progression-free at 2-years from study entry estimated using Kaplan-Meier methods. Per RECIST 1.0 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or equivocal progression of non-target.

Time frame: Disease assessments occurred 8-10 weeks following treatment end then every 4-6 weeks (yr 1), every 8-10 weeks (yr 2), quarterly (yr 3) and semiannually up to 2 yrs since last pt enrolled.

Population: The phase II portion planned to enroll 34 participants including the phase I expansion cohort but the study did not continue beyond phase I.

The Abraxane MTD in combination with carboplatin and concurrent IMRT is determined by the number of participants who experience a dose limiting toxicity (DLT). See subsequent primary outcome measure for the DLT definition. The MTD is defined as the highest dose at which fewer than one-third of participants experience a DLT. If no DLTs are observed then the MTD is not reached but the highest dose may then be the recommended phase II dose.

Time frame: Adverse event assessments occurred weekly on treatment; The observation period for MTD evaluation incorporated the 7 weeks of treatment.

Population: The MTD was not reached on this trial but the recommended phase II dose was the highest dose of Abraxane evaluated.

Dose limiting toxicities (DLT) were defined as treatment-related: 1) grade 3-4 non-hematological toxicity excluding untreated nausea, vomiting and diarrhea; dysphagia, esophagitis, mucositis/stomatitis, dermatitis/rash, 2) Grade 3 or greater febrile neutropenia occurring during chemoradiotherapy, 3) Grade 4 neutropenia lasting \>/= 7 days and 4) Grade 3 thrombocytopenia. Grade 4 toxicities resulting in a treatment breaks \> 7 days were considered DLTs.

Time frame: Adverse event assessments occurred weekly on treatment; The observation period for DLT evaluation incorporated the 7 weeks of treatment.

Population: The analysis dataset is comprised of all treated patients in the dose escalation cohorts.While no DLTs were observed in the first 3 DL 1 patients, the cohort was expanded to 6 patients due to safety and tolerability concerns. Upon further review, it was resolved that the Abraxane dose should not be increased in the setting of concurrent Erbitux.

2-year overall survival is the proportion of patients alive at 2-years from study entry.

Time frame: All patients were followed for survival for a minimum of 2 years. Median survival follow-up was 44.7 months (range 10-70) in this study cohort.

Population: The analysis dataset is comprised of all treated phase I patients. Reporting within dose cohorts is not preferred given the small sample sizes.

The FACT-H&N is a multidimensional, self-report QoL instrument specifically designed for use with head and neck cancer patients. It is comprised of 27 core items from the FACT-G (Version 4), an established survey which assesses the impact of cancer therapy in four domains: physical, social/family, emotional, and functional. \[Cella, D, et al. JCO 1993(11)\]. It is supplemented with a validated measure of 12 site specific items to assess for head and neck related symptoms. \[D'Antonio L, Zimmerman G, et al. Cancer 1996 (77)\] Each item is rated on a 0 to 4 Likert type scale, and then combined to produce subscale scores for each domain, as well as a global QoL score (range: 0-156). Higher scores represent better QoL. The change score is calculated as post-baseline less baseline; therefore, a negative value indicates a decrease in score and correspondingly a decrease in QoL.

Time frame: Baseline and 12 months

Population: The analysis dataset is comprised of patients with evaluable data at the 2 assessment timepoints: baseline and 12 months.

The FACT-H&N is a multidimensional, self-report QoL instrument specifically designed for use with head and neck cancer patients. It is comprised of 27 core items from the FACT-G (Version 4), an established survey which assesses the impact of cancer therapy in four domains: physical, social/family, emotional, and functional. \[Cella, D, et al. JCO 1993(11)\]. It is supplemented with a validated measure of 12 site specific items to assess for head and neck related symptoms. \[D'Antonio L, Zimmerman G, et al. Cancer 1996 (77)\] Each item is rated on a 0 to 4 Likert type scale, and then combined to produce subscale scores for each domain, as well as a global QoL score (range: 0-156). Higher scores represent better QoL. The change score is calculated as post-baseline less baseline; therefore, a negative value indicates a decrease in score and correspondingly a decrease in QoL.

Time frame: Baseline and 24 months

Population: The analysis dataset is comprised of patients with evaluable data at the 2 assessment timepoints: baseline and 24 months.

The FACT-H&N is a multidimensional, self-report QoL instrument specifically designed for use with head and neck cancer patients. It is comprised of 27 core items from the FACT-G (Version 4), an established survey which assesses the impact of cancer therapy in four domains: physical, social/family, emotional, and functional. \[Cella, D, et al. JCO 1993(11)\]. It is supplemented with a validated measure of 12 site specific items to assess for head and neck related symptoms. \[D'Antonio L, Zimmerman G, et al. Cancer 1996 (77)\] Each item is rated on a 0 to 4 Likert type scale, and then combined to produce subscale scores for each domain, as well as a global QoL score (range: 0-156). Higher scores represent better QoL. The change score is calculated as post-baseline less baseline; therefore, a negative value indicates a decrease in score and correspondingly a decrease in QoL.

Time frame: baseline and 4 months

Population: The analysis dataset is comprised of patients with evaluable data at the 2 assessment timepoints: baseline and 4 months.

he FACT-H&N is a multidimensional, self-report QoL instrument specifically designed for use with head and neck cancer patients. It is comprised of 27 core items from the FACT-G (Version 4), an established survey which assesses the impact of cancer therapy in four domains: physical, social/family, emotional, and functional. \[Cella, D, et al. JCO 1993(11)\]. It is supplemented with a validated measure of 12 site specific items to assess for head and neck related symptoms. \[D'Antonio L, Zimmerman G, et al. Cancer 1996 (77)\] Each item is rated on a 0 to 4 Likert type scale, and then combined to produce subscale scores for each domain, as well as a global QoL score (range: 0-156). Higher scores represent better QoL. The change score is calculated as post-baseline less baseline; therefore, a negative value indicates a decrease in score and correspondingly a decrease in QoL.

Time frame: Baseline and 6 months

Population: The analysis dataset is comprised of patients with evaluable data at the 2 assessment timepoints: baseline and 6 months.

Estimated as the time from registration to the date of PEG removal.

Time frame: Assessed until time of PEG removal which was up to 18.4 months in this study cohort.

Population: The analysis dataset is comprised of all patients with date of PEG removal (evaluable). Reporting within dose cohorts is not preferred given the small sample sizes.

Overall response (OR) rate was defined as achieving partial response (PR) or complete response (CR) based on RECIST 1.0 criteria on treatment. Per RECIST 1.0 for target lesions, CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. To be assigned a status of CR or PR, changes in tumor measurements must be confirmed by repeat assessments performed no fewer than 4 weeks after the response criteria are first met. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.

Time frame: The primary re-staging assessment for response occurred 8-10 weeks following completion of treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1).

Population: The analysis dataset is comprised of all treated phase I patients. Reporting within dose cohorts is not preferred given the small sample sizes.