Search

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.

CV 205-502 (octahydrobenzol[g]quinoline), a non-ergot dopamine agonist drug, was administered to 40 patients with hyperprolactinemic syndrome: 16 patients with macroprolactinoma, 14 with microprolactinoma and 10 with non-tumoral hyperprolactinemia. Twenty-four out of 40 patients had previously been treated by surgery and/or bromocriptine, with variable results. All had gonadal dysfunction and 22 patients had galactorrhea. Eight patients with macroprolactinoma had defects of the visual field. Pre-treatment serum PRL levels ranged from 60 to 2050 micrograms/l. The daily dose of CV 205-502 used in this trial ranged from 0.075 to 0.600 mg. After 6-12 months of treatment, serum PRL level decreased in all the patients reaching normoprolactinemia in 31 of them (77.5%) who demonstrated restoration of menses and disappearance of galactorrhea. The remaining nine patients (22.5%) had only a decrease of PRL levels without reaching normoprolactinemia and without any clinical effect. In 12 out of 16 patients with macroprolactinoma not previously surgically treated, a significant tumor shrinkage was shown by means of Computed Tomography and/or Magnetic Resonance Imaging. The disappearance of visual defects was obtained in four out of eight patients. CV 205-502 was tolerated satisfactorily: mild side-effects occurred in four patients in the first week of treatment and spontaneously disappeared, whereas six patients (15%) needed to withdraw the therapy after 6 months because of side-effects. In conclusion CV 205-502 is a potent and well-tolerated drug in the treatment of tumoral and non-tumoral hyperprolactinemic states and is an effective alternative to other dopamine agonists in use today.

Between 1988 and 1992, 60 patients with intermediate and high-grade non-Hodgkin's lymphomas (NHL) were treated with a new multidrug combination chemotherapy including 4'epidoxorubicin (25 mg/m2), etoposide (60 mg/m2), cyclophosphamide (400 mg/m2), administered intravenously (i.v.) on the 1st, 2nd and 3rd day every 4 weeks, prednisone (40 mg/m2) orally for 6 days every 4 weeks, vincristine (1 mg/m2) i.v. and methotrexate (400 mg/m2) i.v. on the 8th day every 4 weeks, vindesine (2.5 mg/m2) and cytarabine (200 mg/m2) on the 15th day every 4 weeks. Patients achieving apparent complete remission (CR) or good partial response (PR) after the 1st cycle of therapy were submitted to three other cycles of the same therapy. Patients failing to respond to the 1st cycle or whose disease progressed despite therapy, were treated with an alternative 2nd line therapy. Seventeen patients (28%) had stage II-II E, 15 (25%) stage III and 28 (47%) stage IV disease. Tumoral mass > 10 cm was found in 28 cases, the presence of extranodal sites (ES) in 32 cases, serum lactate dehydrogenase (LDH) > 240 IU/l in 34 cases, performance status (PS) > or = 2 in 12 cases. CR was obtained in 46 (76.4%) out of the 60 patients. Relapse-free survival (RFS) was 82, 64 and 61% with a median follow-up of 12, 24 and 36 months respectively. No relapse occurred later than 26 months after achievement with CR thus far. Overall survival (OS) was 77% at 12 months and calculated to be 62% and 59% at 24 and 36 months, respectively. Two patients died as a result of the treatment. Reversible myelosuppression was the main toxic effect. One hundred and ten out of the 221 cycles of chemotherapy were delayed because of therapy toxicity. Negative prognostic factors on the RFS and OS were the presence of an advanced stage of disease, a mass larger than 10 cm, the presence of ES, the elevated LDH, the PS > or = 2, the delay of therapy. In conclusion, results obtained using our protocol overlap those from other third generation regimens. Toxicity was also similar. The influence of clinical conditions such as stage of disease, the presence of ES, high LDH level and tumoral mass > 10 cm on the RFS and OS were significant. Principal variables influencing prognosis must be unified to compare results of similar treatments from different institutions.

We describe in detail the current trend using monoclonal antibodies to diagnose ovarian cancer either in vitro or in vivo. The approach with such powerful reagents allows to differentiate in vitro tumor histotypes and to detect in peritoneal washings the presence of a few neoplastic cells which characterize the minimal disease. The detection of elevated sera levels of ovarian cancer-associated antigens, such as CA-125 and TAG-72, allows the monitoring, follow-up of these patients and the response to therapy with great accuracy. We focused our attention on the role in vivo of labelled monoclonal antibodies, mainly for diagnostic purposes. Radioimmunoscintigraphy has been found to be more reliable than CT and US to detect foci of disease mainly in patients already treated by surgery, overcoming all the problems usually encountered with these two procedures.

The authors have analysed the theoretical and clinical implications of a biological approach to radioimmunoscintigraphy (RIS), a new diagnostic technique based on the in vivo reaction between radiolabelled monoclonal antibodies and tumor-associated antigens expressed by the neoplastic cells. The assumption is that, as in all radioisotopic procedures, the radioimmunoscintigraphic image is the expression of differences in concentration (and not in density) between adjacent tissues. This "biological premise" is analysed to demonstrate a possible role of RIS not only in diagnosis but also in prognosis and therapy. A comparison with other imaging procedures and with histopathology, considered as the "gold standard" of the present-day morphological approach to diagnosis, is also discussed. Finally, biological premises, as well as the initial results and prospects regarding the use of high doses of radiolabelled monoclonal antibodies for therapeutic purposes are presented.

Cyclophosphamide (CP) metabolites, rather than the parent compound, show mutagenic activity towards Salmonella typhimurium TA 1535 tester strain when S9 fraction from phenobarbital (PB)-induced rat liver is used as in vitro metabolizing system. On the other hand, inhibition of CP in vitro mutagenicity was observed by adding increasing amounts of beta-carotene (beta-C) to the system. A typical dose-dependent mutagenic response was observed by assaying 24 h urine samples of PB-induced rats injected i.p. with different amounts of CP. Addition of beta-C to urines of CP-treated rats failed to inhibit their mutagenicity. Conversely, a marked decrease in urine mutagenicity was observed when rats were simultaneously treated with the two drugs. These data show that beta-carotene partially inhibits, in vitro and in vivo, CP metabolism via hepatic mixed-function oxidase enzymes to mutagenic species.