6040 Background: Cisplatin is one of the most active chemotherapeutic agents used in the treatment of advanced squamous cell carcinoma of the head and neck (SCCHN). However, its clinical efficacy is limited by its renal- and hematotoxicity profile. In a randomized, multicenter phase III trial, we replaced conventional cisplatin by a liposomal formulation of cisplatin (lipoplatin), and compared the safety and efficacy profiles of patients (pts) in the two treatment arms. Methods: Arm A: 100 mg/m2/d lipoplatin (d 1,8,15) plus 1,000 mg/m2/d 5-FU (d 1–5) q3w for 6 cycles; arm B: 100 mg/m2/d cisplatin (d 1) plus 1,000 mg/m2/d 5-FU (day 1–5) q3w for 6 cycles. Inclusion criteria: histologically confirmed SCCHN, age 18–75, renal function (creatinine clearance >50 ml/min) and primary metastatic disease or progressive SCCHN. Results: 62 pts were randomized, from which 43 pts (39 m; 4 w) were evaluable for outcome and toxicity. In the cisplatin arm hematotoxicity was more frequent (grades I/II: 28 pts, grades III/IV: 2 pts) than in the lipoplatin arm (grades I/II: 15 pts, grades III/IV: 3 pts). The rate of anemia was similar between the treatment arms. 13 pts in the lipoplatin arm experienced renal toxicity with (grade I: 3pts) and (grade II: 10 pts), as measured by a reduction of the creatinine clearance (grade I: 99–75 ml/min; grade II: 74–50 ml/min; grade III: <50 ml/min). Renal toxicity occurred in 8 patients in the cisplatin arm with 1 pt (grade I) and 3 pts (grade II), however 5 pts developed grade III. No renal toxicity grade III was developed in the lipoplatin arm until now. Outcome was as follows: lipoplatin arm: PR: 3 pts; SD: 13 pts; PD: 9 pts; cisplatin arm: PR: 8 pts; SD: 9 pts; PD: 1 pts. Thus, the non-PD pts (PR or SD) was 16/25 (64 %) in the lipoplatin arm vs 17/18 (94%) cases in the cisplatin arm. Conclusions: Liposomal platin seems to reduce both the renal and hematological toxicity as compared to conventional cisplatin to a clinically relevant extent. This reduction of side effects will influence the chance to preserve the dose density of chemotherapy, and thereby, the efficacy of treatment. No significant financial relationships to disclose.
We report our results from the analysis of Doppler measurements of breathing-related fluid flow velocity waveforms in the trachea in human fetuses. Our aim was to determine whether, using the proposed method, reproducible patterns can be recognized over the latter half of gestation. Breathing-related tracheal fluid flow velocity of 47 normal fetuses at 20-39 weeks' gestation were analysed. Colour Doppler was used to document 'streaming' of fluid in the trachea, followed by spectral Doppler to record flow velocity waveforms. More than 40 (median 94; range 42-725) continuous breathing cycles (inspiration+expiration) were obtained in each case. Although breathing-related fetal tracheal fluid flow waveforms were found to be highly variable, we were able to distinguish by visual analysis between a regular and an irregular pattern. Among the regular patterns, we further differentiate between a regular symmetric (sinusoidal type) and a regular asymmetric (deep inspiration with expiratory flow retardation) pattern. The regular pattern occurred consistently in all age groups studied and there were no significant (p<0.05) differences in the occurrence rate of the regular symmetric and asymmetric pattern. The incidence of the regular pattern increased significantly (p<0.05) from 11.74+/-3.38% (mean +/- SEM) at 24-27 weeks to 20.72+/-1.75% at 28-31 weeks of gestation and remained constant thereafter. This study shows that the proposed method can provide detailed information on breathing-related tracheal fluid flow velocity as early as 20 weeks of gestation. The information that a regular symmetric pattern was observed throughout the second half of gestation is important. Hence, a higher standardization of on-going fetal breathing movements studies may be achieved by measuring breathing-related tracheal fluid flow velocity waveform parameters only during this pattern.
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