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OBJECTIVE To assess the feasibility and efficacy of subcutaneous amifostine therapy in patients with head and neck cancer treated with curative accelerated radiotherapy (RT). DESIGN Retrospective study. SETTING University of Lausanne, Lausanne, Switzerland. PATIENTS Thirty-three consecutive patients (male-female ratio, 4.5; median age, 54 years [age range, 39-76 years]). INTERVENTIONS Between November 2000 and January 2003, the 33 patients were treated with curative definitive (n = 19) or postoperative (n = 14) RT with (n = 26) or without (n = 7) chemotherapy. All patients received conformal RT. Fractionation schedule consisted of concomitant-boost (Friday afternoon session) accelerated RT using 70 Gy (2 Gy per fraction) in 6 weeks in patients treated with definitive RT and 66 Gy (2 Gy per fraction) in 5 weeks and 3 days in the postoperative setting. Parotid glands received at least 50 Gy in all patients. Amifostine was administered to a total dose of 500 mg subcutaneously, 15 to 30 minutes before morning RT sessions. RESULTS All patients received their planned treatment (including chemotherapy). Ten patients received the full schedule of amifostine (at least 25 injections), 9 received 20 to 24 doses, 4 received 10 to 19 doses, 5 received 5 to 9 doses, and 5 received fewer than 5 doses. Fifteen patients (45%) did not show any intolerance related to amifostine use. Amifostine therapy was discontinued because of nausea in 11 patients (33%) and hypotension in 6 patients (18%), and 1 patient refused treatment. No grade 3, amifostine-related, cutaneous toxic effects were observed. Radiotherapy-induced grade 3 acute toxic effects included mucositis in 14 patients (42%), erythema in 14 patients (42%), and dysphagia in 13 patients (39%). Late toxic effects included grade 2 or more xerostomia in 17 patients (51%) and fibrosis in 3 patients (9%). Grade 2 or more xerostomia was observed in 8 (42%) of 19 patients receiving 20 injections or more vs 9 (64%) of 14 patients receiving fewer than 20 injections (P = .15). CONCLUSIONS Subcutaneous amifostine administration in combination with accelerated concomitant-boost RT with or without chemotherapy is feasible. The major adverse effect of subcutaneous administration was nausea despite prophylactic antiemetic medication, and hypotension was observed in only 6 patients (18%).Arch Otolaryngol Head Neck Surg. 2006;132:141-145--

•The DNA methylation patterns differ between patients with chronic nociceptive or neuropathic pain.•In the 2 types of pain, differential methylations affect mostly the neuro-musculoskeletal genes.•An epigenetic disturbance of the opioid system is observed in chronic nociceptive pain patients.•An epigenetic disturbance of the GABAergic system is observed in chronic neuropathic pain patients.

Background. The “Patterns of Activity Measure” (POAM-P) is a self-administered questionnaire that assesses “avoidance”, “pacing” and “overdoing” activity patterns in chronic pain patients. Objectives. To adapt the POAM-P to French (“POAM-P/F”) and test its validity and reliability in Chronic Musculo-Skeletal Pain patients (CMSP). Methods. We followed the recommended procedure for translation of questionnaires. Five hundred and ninety five inpatients, admitted to a tertiary rehab center in the French-speaking part of Switzerland for chronic pain after orthopedic trauma, were included (sex ratio M/F = 4.36, mean age 43±12). Face, content and criterion validities, internal consistency and reliability were assessed. Data included: TAMPA Scale for Kinesiophobia (TSK), Chronic Pain Coping Inventory (CPCI), Pain Catastrophizing Scale (PCS), Brief Pain Inventory (BPI), Hospital Anxiety and Depression Scale (HADS). Results. Face and content validities were checked during the translation process. Correlations between POAM-P/F-avoidance and TSK, POAM-P/F-pacing and CPCI-pacing, POAM-P/F-overdoing and CPCI-task persistence were highly significant (r>0.3, p<10-2). The three subscales demonstrated excellent homogeneity (Cronbach’s alpha coefficients > 0.8) and test-retest reliability (Intraclass Correlation Coefficients > 0.8). They correlated very differently with the other scales. Discussion and Conclusion. The three POAM-P/F subscales clearly assess different behaviors in CMSP. The POAM-P/F is a suitable questionnaire for classifying French speaking CMSP into avoiders, pacers or overdoers.

Granulocyte Colony-Stimulating Factor (G-CSF) is regularly used after autologous peripheral blood stem cell transplant (ASCT) to accelerate neutrophil engraftment. The result is a reduction of the number of febrile days, antibiotic use and duration of hospitalization, resulting in a reduction of costs. Randomized trails demonstrated that further cost reduction is obtained by delaying the beginning of G-CSF therapy from day 1 to days 5-7 post transplant without significantly changing the time to neutrophil recovery, despite a trend to better results when the drug was started on day 1. Pegfilgrastim is a sustained duration form of filgrastim administered as a single-fixed s.c. dose, a schedule that is more patient friendly. Moreover, as the drug is given in a single shot, there is no need to delay the therapy to decrease treatment costs. This trial was conducted to assess the efficacy and safety of pegfilgrastim to enhance neutrophil recovery after ASCT.in this bi-institutional phase II trial 40 patients with Multiple Myeloma (N=20), Hodgkin Lymphoma (N=8) and Non-Hodgkin Lymphoma (N=12) were accrued from January 2007 to December 2008. Pegfilgrastim 6 mg s.c. was administered on transplant day 1. Results were compared with a historical control group of 40 patients (20 with myeloma and 20 with lymphoma) treated with filgrastim 5μg/kg/d s.c. starting at median day 7 after transplant (range 3-7). All lymphoma patients (cases and controls) received BEAM as high dose schedule, while the 40 multiple myeloma patients were treted with MEL200. If tandem transplants were planned, only the first procedure was eligible to the study. Differences between groups were estimated by two-sample t-test and Wilcoxon rank-sum test. A two sided p-value of <0.05 was considered statistically significant.case and control populations were statistically similar in terms of age, sex, disease, conditioning regimen, CD34+ cell-dose and number of prior therapy lines. Median time to achieve a neutrophil count > 500/μl was 9.5 vs 11.3 days for case and controls, respectively (p<0.0001); median duration of neutropenia was 5.8 vs 7.4 days (p=0.0001); median time to platelet count > 20000/μl was 11.9 vs 11.4 days (p=0.42); median duration of fever was 3.4 vs 4.6 days (p=0.3); median duration of i.v. antibiotic therapy was 4.2 vs 6.5 days (p=0.0007); median hospitalization duration was 14 vs 14.8 days (p=0.0184, N.S. at t-test). Both groups received an equal number of RBC and platelet transfusions. Pain was present in 12.5% of patients in the experimental group and lasted for a median of 3 days (2-9). No other toxicities related to pegfilgrastim were observed. The control group received a median of 6.5 doses of filgrastim (range 4-10). Market prices per treatment are 2076.75 vs 1534.90 Swiss Francs for pegfilgrastim and filgrastim, respectively.Pegfilgrastim given as a single dose of 6 mg s.c. on transplant day 1 accelerates neutrophil engraftment, shortens the duration of neutropenia and hospitalization and reduces the use of i.v. antibiotics compared to daily filgrastim. The 25% increase in costs when using pegfilgrastim is counterbalanced by a shorter time on antibiotics and a tendency to a shorter time in hospital.Wannesson: AMGEN: Research Funding. Off Label Use: Pegfilgrastim is a pegilated formulation of filgrastim, a reccombinant human granulocyte colony stimulating factor. It has a long half life allowing a single dose treatment instead of multiple repeated doses. In general it has been shown equivalent results comparing to filgrastim in all clinical settings, even if still off-label for some indications, like the post-autologous transplant support (matter of the present abstract). Ghielmini:AMGEN: Research Funding. Ketterer:AMGEN: Research Funding.

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