Comparative efficacy of various treatment regimens for androgenetic alopecia in men

Our understanding of the aetiology of androgenetic alopecia (AGA) has substantially increased in recent years. As a result, several treatment modalities have been tried with promising results especially in early stages of AGA. However, as far as has been ascertained, there is no comprehensive study comparing the efficacy of these agents alone and in combination with each other. One hundered male patients with AGA of Hamilton grades II to IV were enrolled in an open, randomized, parallel-group study, designed to evaluate and compare the efficacy of oral finasteride (1 mg per day), topical 2% minoxidil solution and topical 2% ketoconazole shampoo alone and in combination. They were randomized into four groups. Group I (30 patients) was administered oral finasteride, Group II (36 patients) was given a combination of finasteride and topical minoxidil, Group III (24 patients) applied minoxidil alone and Group IV (10 patients) was administered finasteride with topical ketoconazole. Treatment efficacy was assessed on the basis of patient and physician assessment scores and global photographic review during the study period of one year. At the end of one year, hair growth was observed in all the groups with best results recorded with a combination of finasteride and minoxidil (Group II) followed by groups IV, I and III. Subjects receiving finasteride alone or in combination with minoxidil or ketoconazole showed statistically significant improvement (p<0.05) over minoxidil only recipients. No signifcant side-effects related to the drugs were observed. In conclusion, it is inferred that the therapeutic efficacy is enhanced by combining the two drugs acting on different aetiological aspects of AGA.     

Receptor imaging with 111In-pentreotide and 123I-methoxybenzamide, and inhibition tests with octreotide and bromocriptine of mixed growth hormone/prolactin-secreting pituitary tumors.

We have performed pituitary scintigraphy with 111In-pentreotide (OCT), a somatostatin analogue, and with metoxybenzamide (IBZM) by 123I-IBZM in two patients affected by mixed growth hormone/prolactin-secreting pituitary tumors. Short-term growth hormone (GH) inhibition by a single injection of OCT (100 micrograms s.c.), and short-term prolactin (PRL) inhibition by oral administration of 2.5 mg of bromocriptine (BCR), were also performed in both patients. The first patient, a 26 year old man, showed intense tumor uptake of 123I-IBZM scintigraphy, whereas 111In-OCT scintigraphy showed moderate tumor uptake. Five hours after the BCR inhibition test, a fall of 83% in PRL plasma levels (from 8,336 micrograms/L to 1,417 micrograms/L), and of 91.6% in GH plasma levels (from 39.5 micrograms/L to 3.3 micrograms/L) were observed. OCT inhibition test suppressed GH plasma levels from 36 micrograms/L to 3.5 micrograms/L. The patient was submitted to treatment with BCR and OCT. A dramatic shrinkage of the tumor was seen after six months of therapy. The lesion disappeared one year after the start of therapy. The second patient, a 64 year old man, showed intense uptake at 111In-OCT scintigraphy, while 123I-IBZM uptake was not observed. A test dose of BCR resulted in an acute fall of PRL (from 145 micrograms/L to 118 micrograms/L), but not of GH. A test dose of OCT decreased the GH plasma level from 61 micrograms/L to 4.5 micrograms/L. The patient was submitted to treatment with BCR and OCT that resulted in a computed tomography and magnetic resonance imaging decrease of 45% of tumor volume one year after the start of therapy. Our results suggest that both suppression tests with OCT and BCR, and scintigraphic studies in vivo with 123I-IBZM and 111In-OCT can be predictive for the effectiveness of therapies with dopamine agonists and/or SS-analogs in patients with mixed PRL/GH-secreting pituitary tumors. Further studies are required to evaluate the role of suppressive tests in selecting patients for appropriate clinical treatments.     

A dose-comparative endocrine-clinical study of leuprorelin in premenopausal breast cancer patients

Twelve premenopausal patients with advanced breast cancer were randomised to receive 3.75 or 7.5 mg of a slow release formulation of the luteinising hormone releasing hormone agonist leuprorelin once every 4 weeks. All patients were oestrogen receptor positive or unknown. Serum levels of gonadotrophins and oestrogens were suppressed markedly by both doses. All oestrogen values during treatment were within the postmenopausal range except for a single oestradiol level (274 pmol l-1) in one patient on the lower dose. There was no other indication that this lower dose was less effective as an oestrogen suppressant. There were two objective responders to the 3.75 mg dose and three to the 7.5 mg dose. Toxicity was confined almost entirely to hot flushes which occurred in 11/12 patients. We conclude that the slow release formulation of leuprorelin is effective in breast cancer treatment and that there is no major detriment to the use of the 3.75 rather than 7.5 mg dose.     

Evaluation of TAG-72 as a serum marker in ovarian and breast carcinoma

Tumor Associated Glycoprotein 72 (TAG-72) is common to most epithelial tumors. In this study serum levels of TAG-72 were measured in 36 healthy female subjects, in 94 patients with breast cancer, and in 43 others with epithelial ovarian cancer. More particularly, 27 out of the 94 patients with breast cancer had early disease (Stage I-I; or T 0-2b; N 0-1b; M 0), while the remaining 67 had advanced disease (Stage III-IV; or T 0-4; N 0-3; M 0-1). All the 43 subjects with ovarian cancer were at stage III-IV (FIGO Classification), 12 of whom had minimal disease (lesions less than 2 cm) and the other 31 had bulky disease. 3.5 U/ml being the highest value found in the control group, we arbitrarily assumed 3.85 U/ml (mean +/- 3 SD) as the cut-off limit in this preliminary study. Among the patients with breast cancer, 17 out of the 67 subjects with advanced disease (25.3%) and 1 out of the 27 others with early disease (3.7%) exceeded the TAG-72 cut-off limit. Among the patients with ovarian cancer, 2 out of the 12 subjects with minimal disease (16.7%) and 22 out of the others 31 with bulky disease (70.9%) had TAG-72 levels above cut-off limit. High TAG-72 levels were found in all the histotypes of ovarian cancer including the mucinous type. Preliminary data seem to indicate that in ovarian cancer variations in serum levels of TAG-72 are in agreement with the trend of the disease.(ABSTRACT TRUNCATED AT 250 WORDS)     

A phase II study in advanced gastro-esophageal cancer using epirubicin and cisplatin in combination with continuous infusion 5-fluorouracil (ECF)

PURPOSE:: A phase II study was performed in patients with unresectableor metastatic gastric cancer evaluating the efficacy of a newchemotherapy schedule combining epirubicin and cisplatin witha continuous ambulatory infusion of 5-fluorouracil (ECF). PATIENTS AND METHODS:: One hundred thirty-nine consecutive, previously untreated patientswere given ECF. Of these, 128 had measurable disease. Epirubicin(50 mg/m² i.v.) and cisplatin (60 mg/m² i.v.) were administeredevery three weeks for 8 cycles during a 21 week continuous i.v.infusion of 5-fluorouracil (200 mg/m²/day). In total 773 cyclesof chemotherapy were given. RESULTS:: Objective tumour responses was seen in 91 (71%) of the 128 patientswith measurable disease, of which 15 (12%) had a complete response.Twenty patients with locally advanced disease responding toECF had attempted resection of the primary - 11 (55%) were completelyremoved, 4 of these had no residual tumour in the resected specimen.The overall median survival was 8.2 months with 1 and 2 yearsurvivals of 30% and 10% respectively. Grade 3 or 4 emesis occurredin 13%, stomatitis in 7%, diarrhoea in 4%, infection in 6%,leucopenia in 21% and thrombocytopenia in 8% of patients. Myelosuppressiondelayed treatment in 39 (5%) of the 773 cycles. Six of the 139patients (4.3%) had treatment related deaths. There was no measurablereduction in quality of life during chemotherapy, while 67%of the 66 patients with dysphagia had complete resolution ofthis symptom. CONCLUSIONS:: The ECF regimen displays high anti-tumour activity with moderatetoxicity in patients with gastric cancer and in some cases enabledresection of previously inoperable tumours. chemotherapy, gastro-oesophageal cancer     

Are serial measurements of CA19-9 useful in predicting response to chemotherapy in patients with inoperable adenocarcinoma of the pancreas?

Thirty-nine patients with inoperable adenocarcinoma of the pancreas were studied (27 male, 12 female; median age 60 years, range 39-75 years). All patients received chemotherapy with continuous infusion 5-fluorouracil with intravenous bolus epirubicin followed by cisplatin, repeated every 21 days for a total of six cycles and were evaluable for response. Serum CA19-9 concentrations were obtained at baseline and before each cycle. A rise or fall in the tumour marker was defined as a greater than 15% increase or decrease in the marker on two consecutive occasions 3 weeks apart. A plateau in the tumour marker was defined as a less than 15% decrease or increase on two occasions. Changes in marker expression were compared with serial computerized tomography scanning before treatment and after the third and sixth cycle of chemotherapy. Thirty-five of 39 patients had an elevated CA19-9 (87.9%). Thirteen (36.2%) exhibited a decrease, seven (19.4%) a plateau and 16 (44.4%) patients had a progressive rise in serum CA19-9. The sensitivity of CA19-9 was 67% for predicting a partial response and 86% for progressive disease. The median survival for the 13 patients exhibiting a reduction was 333 days, for the seven patients exhibiting a plateau 253 days and for those who had a progressive rise 185 days. The difference in median survival between the group of patients with > 15% decrease and those with > 15% increase of CA19-9 was significant (P = 0.001). In the cohort of patients who exhibited a reduction in CA19-9, no tumour progression was seen, and the reduction occurred during the first three cycles of treatment. Thus, interval scanning may be avoided in this group of patients.