Phase II evaluation of diaziquone (CI-904, AZQ) in the treatment of human malignant glioma

Summary Diaziquone, a new alkylating agent which crosses the blood brain barrier, has shown a 20% response rate in phase II studies in heavily pretreated patients. We have treated 23 patients at our institution as part of a multicentric phase II European trial of diaziquone. All had histologically proven malignant glioma unequivocally progressing on CT scan. Prior therapy had consisted of surgical excision (13 patients), cobalt radiotherapy to CNS (13 patients), and chemotherapy with nitrosourea derivatives (11 patients). Six patients had no prior therapy. Median age was 42 years (range 22–69) and performance status was 3+ or better. They were treated with monthly courses of diaziquone 5.5 mg/m² I.V. (10 min.) × 5 days. Dosage adjustments were made according to leucocyte and platelet nadirs. Thrombocytopenia was the dose limiting toxicity. Very mild gastrointestinal toxicity was observed. One patient developed hemolytic anemia. One complete response (clinical and CT scan), 7 partial clinical responses (3: > 50%, 4: 25–50%), and 1 disease stabilization (<25%) were documented. The longest response has now lasted over 26 months. These preliminary results show that chemotherapy with diaziquone can achieve a response rate as high as 35% in malignant glioma even in patients previously treated with a chemotherapy regimen including a nitrosourea (four of the seven objective responses were seen in such patients). Diaziquone is well tolerated and deserves further study in the management of malignant glioma. Address for offprints: Dr J Maral, Medical Oncology Service, Hôpital de la Salpetriere, 75651 Paris Cedex 13, France     

The prevalence of hereditary haemochromatosis in a diabetic population

Hereditary haemochromatosis is an under-diagnosed and treatable cause of chronic liver disease. Its prevalence indicates that selective population screening may be worthwhile, but opinion differs as to whether diabetic patients constitute such a group. We studied 727 patients attending a teaching hospital diabetic clinic. On first testing, 7.4% had abnormally high iron indices, but only 3% remained abnormal on retesting. Of these patients, those at high risk were offered liver biopsy for histological assessment and iron assay. Only one had hereditary haemochromatosis, but all had abnormal liver histology--largely steatosis but some with fibrosis. These findings raise questions regarding the true prevalence of this disorder in North- East England, do not indicate that targeted screening of diabetic patients is worthwhile, and incidentally highlight the potential importance of diabetes as a cause of liver disease.      

Prevertebral soft-tissue measurements in cervical spine injury

To clarify normal values for cervical prevertebral soft-tissue measurements and evaluate when they are useful as a marker of cervical spine injury, the prevertebral soft-tissue measurements of 79 control and 57 acutely injured patients were retrospectively compared by two independent observers. The second, blinded, observer made a provisional diagnosis and indicated if increased soft-tissue measurements had assisted in making a diagnosis of injury. If measurements ≥7 mm at C2/3 and ≥21 mm at C6/7 were considered abnormal, a true positive rate of 53% and false positive rate of 5% were observed. The differences between the mean measurements in the control and injured groups were statistically significant (P<0.0001 at C2/3 and P<0.01 at C6). Soft-tissue measurement improved the diagnostic confidence of the blinded second reviewer in 17.5% of the injured group. Analysis of this subgroup revealed a 50% error rate in initial reporting. In all of these cases, the abnormal soft-tissues had been ignored prospectively. Routine measurement of the prevertebral soft tissues is a simple procedure that may provide an important clue to subtle cervical spine injury.     

Psoralen–ultraviolet A vs. narrow-band ultraviolet B phototherapy for the treatment of vitiligo

BACKGROUND: Although many treatment modalities have been tried for the treatment of vitiligo, none is uniformly effective. Psoralen phototherapy (psoralen ultraviolet A (PUVA)) is established as efficacious treatment for vitiligo. Recently, narrow-band UVB (NBUVB) has been reported to be an effective and safe therapeutic option in patients with vitiligo. OBJECTIVE: To compare the efficacy of PUVA and NBUVB in the treatment of vitiligo. DESIGN AND SETTING: Retrospective analysis of 69 patients with vitiligo who were treated either with PUVA or NBUVB at the pigmentary clinic of the Dermatology Department of the Postgraduate Institute of Medical Education and Research, Chandigarh, India. OUTCOME MEASURES: The following variables were compared between the two groups of patients: repigmentation status, number of treatments for marked to complete repigmentation in existing lesions, appearance of new lesions or increase in size of existing lesions, adverse effect of therapy, stability of repigmentation and colour match. RESULTS: In PUVA-treated group, 9 patients showed marked to complete repigmentation (23.6%) and 14 patients showed moderate improvement (36.8%), whereas in NBUVB-treated group, 13 patients showed marked to complete repigmentation (41.9%) and 10 patients showed moderate improvement (32.2%). A statistically significantly better stability and colour match of repigmentation with surrounding skin was seen in NBUVB-treated patients. CONCLUSION: We showed that NBUVB is more effective than PUVA and repigmentation induced with NBUVB is statistically significantly more stable.