goserelin and Pancreatic-Neoplasms

The two hormone analogues octreotide and goserelin have been shown to decelerate growth of human pancreatic cancer in vitro and in vivo. The objective of this pilot study was to investigate the efficacy and toxicity of the combination of these two agents in patients with advanced pancreatic cancer. Octreotide was injected subcutaneously in dosages increasing weekly, starting with 50 micrograms twice daily, until the level of maintenance therapy of 500 micrograms three times a day was reached. In addition, 3.8 mg goserelin acetate was administered subcutaneously at monthly intervals. A median of 7 cycles (range 1-27 cycles) were applied; 13 out of 14 patients entered into the study were evaluable for response and all 14 were evaluated for toxicity. In one patient with initially non-resectable pancreatic cancer, systemic therapy yielded a partial remission lasting 9 months. The degree of tumour regression then allowed a consecutive macroscopic radical tumour resection followed by an additional 6 months of no evidence of disease while the same drug combination was continued. In an additional 9 patients, no change of disease was observed, in some cases for a remarkably long time (up to 27 months). Nevertheless, the objective response rate of 7% (95% confidence interval 0 +/- 21%) was low. In 5 patients a clear improvement in their performance status was seen soon after the start of therapy; 3 patients showed progression of the disease at first evaluation or earlier and 1 patient was not evaluable at the time of study assessment. According to the product-limit method of Kaplan and Meier, the time to progression was 3.0 +/- 1.8 months [median +/- asymptotic standard error (ASE)] and overall survival was 6.0 +/- 1.5 months (median +/- ASE). Toxicity was rare and only of mild to moderate degree. Overall, the regimen under investigation did not meet the criteria for sufficient antitumoural effectiveness. Nevertheless, this study reinforces the concept that pancreatic cancer is principally responsive to endocrine therapy and therefore the further investigation of hormonal manipulation seems worth while in the future.

Topics: Aged; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Female; Goserelin; Humans; Male; Middle Aged; Neoplasm Staging; Octreotide; Pancreatic Neoplasms; Pilot Projects

Eighteen consecutive patients with measurable locally advanced or metastatic pancreatic adenocarcinoma were treated with goserelin (Zoladex) 3.6 mg subcutaneously every 4 weeks. Hydrocortisone 20 milligrams twice daily was commenced with the second injection of goserelin. Objective tumour response was monitored by computerised tomography of the abdomen. There was no objective remission in disease sites. Serial measurements of serum tumour markers showed no reduction in serum CA 19-9 and CA 195 concentrations. The median duration of survival of all cases was 5 months. Administration of goserelin resulted in significant reductions in oestradiol, testosterone, androstenedione in males and reductions in FSH and LH in both males and females. The addition of hydrocortisone resulted in further reductions of androstenedione and testosterone levels in males. Thus goserelin showed no anti-tumour effect, but concentrations required for direct inhibitory effects may be higher than those required to produce effects on hormone suppression.

Topics: Adenocarcinoma; Adult; Aged; Androgens; Androstenedione; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Estradiol; Female; Follicle Stimulating Hormone; Goserelin; Humans; Hydrocortisone; Luteinizing Hormone; Male; Middle Aged; Pancreatic Neoplasms; Testosterone

Recently non-controlled clinical trials reported encouraging results using a suppressive endocrine treatment in patients with unresectable pancreatic cancer. In this study 15 patients were given an LHRH analogue every 4 weeks (goserelin 3.6 mg), while 18 patients with advanced stage pancreatic carcinoma were given only symptomatic therapy. All patients treated with goserelin had sexual hormone suppression. Follow-up included abdominal ultrasound or computed tomography scan every 3 months; Ca 19-9 assay and routine laboratory blood tests were performed every month. No partial or complete response, no performance status or Ca 19-9 level changes were found. No significant difference in survival was seen in the two groups of patients. This study suggests that goserelin is unlikely to have a major influence on the survival of patients with advanced pancreatic carcinoma and casts further doubt upon the hormone-dependence of this neoplasm.

Topics: Aged; Antigens, Tumor-Associated, Carbohydrate; Buserelin; Female; Gonadal Steroid Hormones; Gonadotropins, Pituitary; Goserelin; Humans; Male; Middle Aged; Pancreatic Neoplasms; Prospective Studies; Survival Analysis

We studied the effects of hormonal manipulation by orchiectomy, alone or in combination with the aromatase inhibitor aminoglutethimide (AGT), and by luteinizing hormone-releasing hormone agonist (LH-RH-A) (goserelin) treatment on the development of early putative (pre)neoplastic lesions induced in the pancreas of rats and hamsters by azaserine and N-nitrosobis(2-oxopropyl)amine respectively. Treatment of the animals started 1 week after the last injection with carcinogen and continued for 4 months. Orchiectomy caused a significant inhibition of growth of acidophilic atypical acinar cell nodules in the rat model, whereas surgical castration did not show an effect in the hamster model. In rats, but not in hamsters, orchiectomy resulted in a significant decrease in body weight and in absolute, but not relative pancreatic weight. Treatment of the animals with AGT or goserelin did not cause a significant effect on the development of either putative preneoplastic acinar lesions in rat pancreas or early ductular lesions in hamster pancreas. Hamsters showed clearly higher plasma epidermal growth factor (EGF) and insulin-like growth factor 1 (IGF-1) concentrations than rats, while plasma testosterone levels were significantly lower. Plasma EGF and IGF-1 levels decreased with increasing age in both control and treatment groups. Compared to controls there were no clear unequivocal effects of treatment on EGF, IGF-1 and gastrin levels. Plasma testosterone levels decreased by orchiectomy and LH-RH-A treatment. In rats hormone-induced effects on food intake and altered nutritional status might be important with respect to the development of carcinogen-induced preneoplastic pancreatic lesions.

Topics: Aminoglutethimide; Animals; Azaserine; Body Weight; Buserelin; Carcinogens; Cricetinae; Epidermal Growth Factor; Gastrins; Goserelin; Male; Mesocricetus; Nitrosamines; Orchiectomy; Organ Size; Pancreatic Neoplasms; Precancerous Conditions; Rats; Rats, Inbred Strains; Somatomedins; Testosterone

Ten patients with non-extirpable adenocarcinoma of the pancreas received monthly subcutaneous implantations of the LHRH analogue goserelin. Subjective improvement (diminished abdominal pain and/or weight gain) occurred within 3 months in seven patients and persisted until about 2 months before death. The treatment was well tolerated by the patients. This preliminary study seems to warrant further investigation of goserelin in the management of pancreatic cancer.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Buserelin; Drug Implants; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Middle Aged; Pancreatic Neoplasms; Prospective Studies