Phase II trial of combretastatin A4 phosphate, carboplatin, and paclitaxel in patients with platinum-resistant ovarian cancer.

BACKGROUND: A previous dose-escalation trial of the vascular disrupting agent combretastatin A4 phosphate (CA4P) given before carboplatin, paclitaxel, or both showed responses in 7 of 18 patients with relapsed ovarian cancer. PATIENTS AND METHODS: Patients with ovarian cancer that had relapsed and who could start trial therapy within 6 months of their last platinum chemotherapy were given CA4P 63 mg/m(2) minimum 18 h before paclitaxel 175 mg/m(2) and carboplatin AUC (area under the concentration curve) 5, repeated every 3 weeks. RESULTS: Five of the first 18 patients' disease responded, so the study was extended and closed after 44 patients were recruited. Grade ≥2 toxic effects were neutropenia in 75% and thrombocytopenia in 9% of patients (weekly blood counts), tumour pain, fatigue, and neuropathy, with one patient with rapidly reversible ataxia. Hypertension (23% of patients) was controlled by glyceryl trinitrate or prophylactic amlodipine. The response rate by RECIST was 13.5% and by Gynecologic Cancer InterGroup CA 125 criteria 34%. CONCLUSIONS: The addition of CA4P to paclitaxel and carboplatin is well tolerated and appears to produce a higher response rate in this patient population than if the chemotherapy was given without CA4P. A planned randomised trial will test this hypothesis.

A Phase Ib trial of CA4P (combretastatin A-4 phosphate), carboplatin, and paclitaxel in patients with advanced cancer.

BACKGROUND: The vascular disrupting agent combretastatin A4 phosphate (CA4P) causes major regression of animal tumours when given as combination therapy. METHODS: Patients with advanced cancer refractory to standard therapy were treated with CA4P as a 10-min infusion, 20 h before carboplatin, paclitaxel, or paclitaxel, followed by carboplatin. RESULTS: Combretastatin A4 phosphate was escalated from 36 to 54 mg m(-2) with the carboplatin area under the concentration curve (AUC) 4-5, from 27 to 54 mg m(-2) with paclitaxel 135-175 mg m(-2), and from 54 to 72 mg m(-2) with carboplatin AUC 5 and paclitaxel 175 mg m(-2). Grade 3 or 4 neutropenia was seen in 17%, and thrombocytopenia only in 4% of 46 patients. Grade 1-3 hypertension (26% of patients) and grade 1-3 tumour pain (65% of patients) were the most typical non-haematological toxicities. Dose-limiting toxicity of grade 3 hypertension or grade 3 ataxia was seen in two patients at 72 mg m(-2). Responses were seen in 10 of 46 (22%) patients with ovarian, oesophageal, small-cell lung cancer, and melanoma. CONCLUSION: The combination of CA4P with carboplatin and paclitaxel was well tolerated in the majority of patients with adequate premedication and had antitumour activity in patients who were heavily pretreated.

Use of thoracic impedance sensors to screen for sleep-disordered breathing in patients with cardiovascular disease.

Screening patients for the possibility of sleep apnoea, one of the most common forms of sleep-disordered breathing, requires measurement of respiration. We propose a simple method to estimate the amplitude modulation of a respiratory tidal volume, using a semi-quantitative measure of respiration based on thoracic impedance (TI). Because respiratory volume changes may be accommodated by varying displacements of the rib cage (RC) and abdomen (AB), the latter produced by outward motion of the diaphragm, it is necessary for any useful measure of respiration to be closely related to both RC and AB displacements. Because the relative contributions of RC and AB displacements to respiratory tidal volume vary in different body positions, the present measurements were recorded from subjects in supine, and right and left lateral decubitus postures. We observed a clear linear relationship between TI and both RC and AB signals in all three body positions. There were no statistically significant differences between observed relationships between TI and AB and between TI and RC, and these relationships were independent of the body position. TI sensors appear to be a useful candidate for a simple method of screening for sleep apnoea, especially in a cardiology clinical setting. Further investigation is warranted for the refinement of algorithms to detect changes in amplitude modulation occurring with apnoeas and to remove artefacts due to gross body movements.

Does respiration perturb body balance more in chronic low back pain subjects than in healthy subjects?

OBJECTIVE: To determine whether body balance is perturbed more in low back pain patients than in healthy subjects, under the concept of posturo-kinetic capacity. DESIGN: Comparison of posturographic and respiratory parameters between low back pain and healthy subjects. BACKGROUND: It has been demonstrated that respiratory movements constitute a perturbation to posture, compensated by movements of the spine and of the hips, and that low back pain is frequently associated with a loss of back mobility. METHOD: Ten low back pain patients and ten healthy subjects performed five posturographic tests under three different respiratory rate conditions: quiet breathing (spontaneous), slow breathing (0.1 Hz) and fast breathing (0.5 Hz). RESULTS: Intergroup comparison showed that the mean displacements of the center of pressure were greater for the low back pain group, especially along the antero-posterior axis, where respiratory perturbation is primarily exerted. Inter-condition comparison showed that in slow and fast breathing relatively to quiet breathing, the mean displacement of the center of pressure along the antero-posterior axis was significantly increased only for the low back pain group. CONCLUSION: According to the results, respiration presented a greater disturbing effect on body balance in low back pain subjects. RELEVANCE: This study provides information on the causes of the impaired body balance associated with chronic low back pain, which could be used to improve treatment strategy.

Does body stability depend on postural chain mobility or stability area?

The purpose of this study was to examine whether postural stability depends only on the support base perimeter, that is the stability area, when body balance is perturbed by respiration. To this end, seven normal subjects were asked to breathe quietly, breathe deeply and to hold their breath (apnoea). They were asked to maintain a standing posture (Sta), and two sitting postures differing by the ischio femoral contact with the seat (Sit100 and Sit30). In other words, these three postures differed not only by the stability area, but also by pelvis mobility. The thoracic perimeter, displacement of the centre of pressure (CP) and iliac crest acceleration (Ah), taken as an index of pelvis mobility, of seven normal subjects were recorded. The results showed that the sway path (SP) was longer in seated subjects than in standing ones, and in Sit100 than in Sit30. The distance between the CP extreme positions (Delta Xp) varied in the opposite direction to SP. Iliac crests and thoracic displacements were shown to be in phase in Sit condition, and did not display any particular pattern in Sta. It was concluded that postural steadiness depends on the postural chain mobility in addition to stability area. As pelvis and lumbar column mobility are related, it is proposed that both contribute to postural chain mobility, owing to respiratory perturbation being compensated.

Scaling behavior in beta-wave amplitude modulation and its relationship to alertness.

We performed an experimental study of beta waves occurring in human electroencephalographic signals obtained from six healthy subjects that were monitored during the performance of a task requiring attention to auditory signals. We use wavelet analysis to study whether the fluctuations in the modulation of the beta-wave amplitude related to an indirect measurement of alertness. We found that these fluctuations exhibit a power-law behavior. When the level of alertness dropped, the associated exponent was found to increase, reflecting the fact that long-range correlations grow rapidly within the system. We also studied the fluctuations of amplitude modulation for alpha and theta waves, for which we did not find a power-law behavior.