摘要:

Twenty-two pre-menopausal evaluable patients with advanced breast cancer (median age 39 years; ER positive 19, unknown three; prior adjuvant chemotherapy 16) were treated with the LHRH agonist goserelin depot (Zoladex*). Serum levels of 17 β-estradiol and progesterone were suppressed by goserelin within 3–4 weeks of therapy, while serum leuteinizing hormone and follicle stimulating hormone titers remained in the low level of the normal range. Complete or partial response was documented in seven of 22 cases (32%) and occurred in all major sites of disease. Tumor response was documented in women regularly menstruating at the start of therapy. Median time to disease progression was 23 weeks; median duration of response was 64 weeks; overall survival was 141 weeks. Zoladex was well tolerated: only hot flushes in 82% and reversible cutaneous plgmentation in the site of injection in 45% of the patients were observed. In our experience the activity of Zoladex was comparable to that of oophorectomy, without the psychological trauma and the morbidity related to surgical castration.

ISSN:0959-4973    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

The water-soluble organometallic complexcis-[Pt(Me)2(Me2SO)2] (Me = methyl; Me2SO = dimethyl sulfoxide) (cis-dimethylplatinum(II); CDMP) was evaluated for its toxicity on the rat and for its efficacy against two tumors of this animal: the Yoshida ascites sarcoma and the TSsarcoma of Guérin. The lethal dose for 50% of normal animals was 46.4 mg/kg; the predominant toxic effects were loss of weight, decrease in leukocytes and necrosis of the kidneys after l.v. or of the liver after l.p. administration. Doses of drug varying from 2 to 40 mg/kg were administered once by l.p., l.v., l.m. and intra-tumor (l.t.) route from 1 to 7 days after l.p. injection of 106Yoshida ascites sarcoma cells and s.c. implantation of approximately 300 mg of TSsarcoma of Guérin. The compound showed anti-tumor activity increasing both the average life span and survival of the rats. A comparison between the therapeutic properties of the title complex with those ofcis-[PtCl2(NH3)2] (CDDP) reveals thatcis-dimethylplatinum(II) exhibits the same anti-tumor activity associated with 6 times reduced toxicity.

ISSN:0959-4973    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Twelve patients received intrapleural instilments of the cytostatic agent mitoxantrone in a total dosage of 30 mg for locoregional palliative therapy of malignant pleural effusion. Effusion could be stopped for a mean period of 3.2 months in 11 patients.

ISSN:0959-4973    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

The pharmacokinetics of ifosfamide were studied in 20 patients with soft tissue and bone sarcomas. Drug was administered as a 30–60 min i.v. infusion at 1.2 or 2.0 mg/m2/day for five consecutive days. Some patients also received 1.5 g/m2ofN-acetylcysteine (NAC) administered 3 times per day during the course of therapy. NAC had no effect on ifosfamide pharmacokinetics. There were significant differences in plasma half-life, area under the concentration–time curve and plasma clearance on day 1 versus day 5 of ifosfamide administration. Myelosuppression and granulocytopenia correlated better with day 1 versus day 5 ifosfamide pharmacokinetics suggesting that the alteration of ifosfamide pharmacology with multiple dosing has a significant effect on drug activity.

ISSN:0959-4973    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

The effects of two new Ru(III) complexes, [mer-RuCl3(DMSO)2lm]° and Na[trans-RuCl4(DMSO)lm], were investigated on primary tumor growth and on the survival time using three solid metastasizing tumors of the mouse: Lewis lung carcinoma, B16 melanoma and MCa mammary carcinoma. Na[trans-RuCl4(DMSO)lm] appears to be the most promising compound, in that: (1) it is soluble in water and therefore easy to handle in comparison with the neutral species [mer-RuCl3(DMSO)2lm]° or to the already described BBR2382; (2) similarly to cisplatin, though at a lower level, it reduces tumor growth in its primary site in each tumor model employed; (3) unlike cisplatin, it increases the life span of tumor-bearing hosts in all tumors used, independently of the effects on primary tumor growth; and (4) it is also effective in reducing spontaneous metastasis formation when the effects on primary tumor growth are completely absent. Dimethylsulfoxide (DMSO), used for solubilizing poorly water-soluble compounds (i.e. [mer- RuCl3(DMSO)2lm]°) or for stabilizing the compound in the solution before injection (i.e. Na[trans-RuCl4(DMSO)lm]), reduces the anti-tumor potency. Conversely, the antitumor effects of Na[trans-RuCl4(DMSO)lm] are more pronounced in mice hydrated with isotonic saline. We conclude that Na[trans-RuCl4(DMSO)lm] is a good candidate for further investigations aimed at ascertaining the mechanism of the anti-metastatic activity and of the positive effects on survival time of mice bearing solid metastasizing tumors.

ISSN:0959-4973    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Thein vitrodrug sensitivity of gastric cancer tissues obtained from 40 patients with advanced cancer was compared in terms of the pathological classifications which were assigned according to the General Rules for the Gastric Cancer Study in Surgery and Pathology in Japan. Cases of poorly differentiated adenocarcinoma which had penetrated the serosa were evaluated using the succinate dehydrogenase inhibition (SDI) test for determining thein vitrochemosensitivity. The sensitivity of the stage III group to cisplatin was higher than that of the stage IV group. Although there were no statistical differences in drug sensitivities according to macroscopic findings (Borrmann's classification), the expanding growth type was more susceptible that the infiltrating type to cisplatin, aclacinomycin A (ACR) and carboquone (CQ) microscopically. In cases of lymph node metastasis [n(+)] the sensitivity to cisplatin, ACR, CQ, adriamycin and mitomycin C was less than in those with or without primary lymph node metastasis [n(-)]; lymphatic invasion in the gastric wall (ly) was a significant factor linked to drug resistance. Our findings indicate that the evaluation of tumor pathology is important in predicting the chemosensitivity of poorly differentiated gastric cancers.

ISSN:0959-4973    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

We studied 96 patients with superficial tumors of the urinary bladder treated by transurethral resection in order to investigate the value of IntravesicalCorynebacterium parvum(CP) to prevent recurrences. In 52 cases, two vials (2 ml, 4 mg CP) diluted in 60 ml buffer saline were intravesically administered weekly 12 times and then monthly for a period of 2 years. All patients were studied in a 3 year follow-up by cytology, histology and endoscopy. Recurrences were observed in 21.1% of cases in the CP treated group and in 54.5% of cases in the untreated group. CP immunostimulation is less effective in preventing recurrences in patients with malignant cells as indicated by urine smears in the post-operative period. Morphological changes of the bladder wall due to CP administration in patients without recurrences are described. Chronic lymphocyte infiltrate appears to be an essential event for the action of CP as an adjuvant therapy in urinary bladder cancer.

ISSN:0959-4973    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Ilmofosine (BM 41.440, 1-hexadecylthio-2-methoxymethyl-rac-glycero-3-phosphocholine) is a synthetic alkyl lysophospholipid analog with activity against a variety of tumor modelsin vitroandin vivo.The i.v. form is presently undergoing early clinical investigation in phase 1 trials. In order to help define types of tumors that might be clinically sensitive to this agent we have studied the anti-tumor effects of ilmofosine against a variety of freshly explanted human tumor specimens using anin vitrosoft agar cloning system. Final concentrations of 1.0–30 μg/ml were used in continuous incubations experiments. Of 348 specimens tested, 134 (39%) were evaluable for determination of tumor growth modulating activity. The most common tumor types recruited included non-small cell lung, breast, colorectal, ovarian, renal cell cancer and melanoma. A concentration-dependent increase in the frequency of inhibited tumor specimens was observed with 6/134 (4%) sensitive specimens at 1 μg/ml as compared with 113/133 (85%) sensitive specimens at 30 μg/ml (pin vitro.Clinical phase II trials with Ilmofosine including the tumor types within vitrosensitivity are warranted if adequate plasma concentrations of this agent can be reached in patients.

ISSN:0959-4973    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

The therapeutic response and toxic effects of chemotherapy using several doses of doxorubicin in conventional solution form or bound to an Ion-exchange resin were compared in a rat tumor model, to assess the relationship of drug dose to therapeutic efficacy and associated toxicity. Single bolus injections of 3.0, 4.5, 6.0, 7.5 and 9.0 mg/kg were administered via the abdominal aorta to rats bearing hindlimb tumors. Tumor size was measured serially and the growth rates of treated groups were compared with a control growth curve. In addition, the effect of empty microspheres on tumor growth rate was assessed. The levels of circulating white blood cells were measured and compared to control levels to provide an indication of the severity of bone marrow toxicity experienced by each form of treatment. Finally, any difference in the distribution of doxorubicin to tumor, hindlimb and cardiac tissue following administration of doxorubicin as free drug or on microspheres was ascertained. Empty Ion-exchange resin exerted a small although significant detrimental effect on tumor growth which may be explained by the embolization of microspheres in the precapillary blood vessels of the tumor resulting in a transient delay in tumor growth rate. The lowest dose of doxorubicin produced a significantly better therapeutic response when administered in the free drug form, but higher doses elicited an equivalent delay in tumor growth for both drug microsphere and free drug groups in a dose-dependent manner, with the maximum anti-tumor response occurring at the highest dose. Treatment with free doxorubicin at high doses resulted in significant reductions of circulating white blood cells suggesting the occurrence of bone marrow toxicity. However, addition of Ion-exchange microspheres evinced no significant change in white cell count. Consistently higher levels of doxorubicin were present in the normal hindlimb and tumor tissue of microsphere treated animals over a period of 96 h, indicating prolonged release of drug from the microsphere matrix. Conversely, there was a reduction in the amount of doxorubicin present in cardiac tissue of drug microsphere treated animals compared to free drug treated animals shortly after treatment. In summary, the administration of doxorubicin on Ion-exchange microspheres reduced bone marrow toxicity without altering cytotoxic function and demonstrated the potential of microspheres in the prevention of long-term cardiac toxicity.

ISSN:0959-4973    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

2,3-Dihydrophthalazine-1,4-dione derivatives demonstrated potent cytotoxicity against the growth of murine leukemia cells and human single cell suspension, i.e. Tmolt3leukemia and HeLa-S3, as well as colon adenocarcinoma and KB nasopharynx. However, only select compounds demonstrated activity against bronchogenic lung, osteosarcoma and glioma growth. 2,3-Dihydrophthalazine-1,4-dione was activein vivoagainst L1210 leukemia, Lewis lung and Ehrlich ascites carcinoma growth. In L1210 cells the agents inhibited both DNA and RNA synthesis, and a few of the compounds were capable of inhibiting protein synthesis at 3 times their ED50values. When 2,3-dihydrophthalazine-1,4-dione andN-butyl-2,3-dihydrophthalazine-1,4-dione were examined for their mode of action in the L1210 lymphoid leukemia cells, the sites of inhibition by the agents appear to be thede novopurine pathway at the enzymes IMP dehydrogenase and PRPP amido transferase. IMP dehydrogenase activity was inhibited at least 45% by 45 min at 100μM concentration of drugs whereas the remaining enzymes that were affected by the drugs were not inhibited as early. Secondary sites were dihydrofolate reductase and thymidylate synthetase. The d(NTP) levels were also reduced specifically dATP and dCTP levels.

ISSN:0959-4973    

出版商:OVID    

年代:1992

数据来源: OVID