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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diethyldithiocarbamate (DDTC) has been shown to ameliorate the myelosuppression induced by the platinum cancer chemotherapeutic drugs in mice. Optimal drug scheduling for DDTC and cis-diammine(cyclobutanedicarboxylato)platinum(II) (CBDCA) has been determined in C57BL/6 x DBA/2 F1 mice, using the pluripotent stem cell assay to assess hematological toxicity. DDTC, at doses of 0.3 to 300 mg/kg given 3 h after 60 mg/kg CBDCA, tripled the number of proliferating spleen colony-forming units compared to treatment with CBDCA alone. No significant difference in efficacy was noted among these doses. DDTC, at the lowest myeloprotective dose (0.3 mg/kg), was most active when administered from 1 to 3 h after CBDCA. The combination of DDTC with CBDCA in vivo did not alter the clonogenic survival of L1210 cells compared to CBDCA alone. CBDCA depressed both bone marrow and tumor cell DNA synthesis. DDTC given 3 h after CBDCA hastened the recovery of DNA synthesis only in marrow cells; the addition of DDTC to CBDCA did not alter DNA synthesis in tumor cells. DDTC alone did not significantly affect DNA synthesis in either normal or tumor cells. These results suggest that the mechanism of DDTC myeloprotection involves stimulation of bone marrow cell proliferation and that the selectivity of DDTC is based upon the absence of stimulation in tumor cells.
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PMID:Diethyldithiocarbamate modulation of murine bone marrow toxicity induced by cis-diammine(cyclobutanedicarboxylato)platinum (II). 255 48

A multi-center, open trial was conducted to determine the maximal tolerable dose of carboplatin in combination with conventional doses of both etoposide and an anthracycline for the treatment of previously untreated small cell lung cancer (SCLC) patients. Ninety-five patients [48 with limited disease (LD) and 47 with extensive disease (ED)] received a total of 376 courses of treatment. Carboplatin was given on day 1 at a dose of 250 mg m-2 in 60 courses, 300 mg m-2 in 69, 330 mg m-2 in 236 and 350 mg m-2 in 11, with 120 mg m-2 etoposide on days 1, 3 and 5 and either 40 mg m-2 adriamycin or 60 mg m-2 epirubicin on day 1. Epirubicin was not administered before carboplatin reached the dose of 330 mg m-2. Courses were repeated every 3 weeks. The main toxicity was hematological. The first course of therapy induced a dose-dependent decrease of leucocyte, neutrophil and platelet counts: all patients, except one, who received 350 mg m-2 carboplatin had a neutropenia below 200 microliters-1 and a thrombopenia below 100,000 microliters-1. Three patients died of septicemia. Other toxicities were well tolerated. After three courses, patients were re-staged by performing a mandatory fiberoptic bronchoscopy and a thoracic computed axial tomography (CAT). The overall objective response rate for 86 evaluable patients was 91% (98% for LD) with 21% complete remissions (30% for LD). All 23 hepatic and six brain sites, evaluable after chemotherapy alone, responded.(ABSTRACT TRUNCATED AT 250 WORDS)
Med Oncol Tumor Pharmacother 1989
PMID:Carboplatin in association with etoposide and either adriamycin or epirubicin for untreated small cell lung cancer: a dose escalation study of carboplatin. UCL Clinical Oncology Group. 255 61

Animal models are important to evaluate new treatment modalities. In the present paper a new animal model is described, in which the effects of intraperitoneal (i.p.) administration of cytostatic drugs on cancers restricted to the peritoneal cavity can be studied. The tumor cell line used is a chemically induced carcinoma (CC531), sensitive in vitro to cisplatin (cDDP), carboplatin (CBDCA), 5-fluorouracil (5-FU), doxorubicin and mitoxantrone. Three to 5 weeks after i.p. inoculation of 2 x 10(6) CC531 cells, 80% of Wag/Rij rats develop small tumor nodules on peritoneal surfaces. Both tumor size and localization at this time are comparable to the human situation, especially to cases of minimal residual disease ovarian carcinoma. The model has been used to determine the usefulness of i.p. treatment in comparison to i.v. Changing the route of administration of cDDP from i.v. to i.p. increases tumor platinum concentrations and prolongs survival. The model offers the possibility to study drug pharmacokinetics and tumor drug penetration related to i.p. drug administration.
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PMID:Intraperitoneal tumor growth and chemotherapy in a rat model. 263 67

In the present study, comparison of the therapeutic effects of CDDP and the analogues (CBDCA, 254S, DWA2114R and NK121) on human gynecological carcinomas transplanted into nude mice (uterine cervical cancer; UZ-1-N, endometrial cancer; UE-1-N, ovarian cancer; OCl-1-N, OS-4-N and OS-8-N) was made. CDDP (5 mg/kg), CBDCA (50 mg/kg), 254S (25 mg/kg), DWA (50 mg/kg) and NK121 (18 mg/kg) were administered intraperitoneally every four days at three doses. Simultaneously the tumor size and the body weight were measured and the peripheral WBC and BUN were examined. The results were as follows: 1) The administration of 254S caused a marked inhibition of the tumor growth against all xenografts into nude mice. 2) CDDP and CDDP analogues except 254S were not effective against UE-1-N, but in this xenograft antitumor activity of 254S was remarkable. 3) With 254S, there were a decrease in body weight and the peripheral leukopenia and the elevation of BUN level were more severe. Although 254S has severe side effects, 254S is seemed to be recommendable for the treatment of gynecological malignancies.
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PMID:[Comparative studies of the antitumor activities of CDDP and the analogs--using gynecological carcinomas transplanted into nude mice]. 264 7

An equi-toxic dose of CDDP and its analogues (254-S, NK-121, CBDCA and DWA-2114 R) was administered to rabbits and S.180 bearing mice, and the pharmacokinetics were studied. Blood levels: Plasma total platinum (Pt) curves of 5 drugs decreased, showing a biphasic function. The shortest t 1/2 alpha and the longest t 1/2 beta were observed in CDDP group, which correlated with the rate of protein binding (CDDP greater than DWA-2114R greater than NK-121 greater than CBDCA greater than 254-S). Tissue distribution: The tissue levels of Pt decreased slowly, and showed a similar pattern among 5 drugs. The highest level was observed in the kidney, liver and skin, with a moderate high level in the tumor, lung, spleen and thymus, followed by the heart, pancreas, stomach, intestine, muscle and testis in that order. The lowest level was in the brain in S.180 bearing mice.
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PMID:[Pharmacokinetics of new cisplatin analogues in experimental animals]. 265 24

Since the introduction of Cisplatin (CDDP) into clinical practice in 1972, CDDP has assumed an important role in the treatment of various tumors. But its renal toxicity has been proved to be a dose limiting factor. Thus the total number of courses which may be given is limited. For this reason, efforts have been made to develop CDDP analogues with reduced toxicities, especially renal toxicity, and more enhanced antitumor activity, and they are now reaching the clinical testing phase. Among them Carboplatin (CBDCA), 254-S, DWA 2114R and NK 121 have been well studied. These analogues were noted to be less nephrotoxic, but more myelosuppressive than CDDP in preclinical analysis. As for cytotoxicity, their inhibitory effects on tumor growth in murine experimental system were similar or more to that of CDDP. Due to these data clinical trials have been carried out. Phase I studies have shown that these analogues are relatively free of renal toxicity as evaluated in preclinical studies and that their dose limiting factor is myelosuppression. Estimation of cross resistance to CDDP and antitumor spectrum have been studied at phase II trials which are ongoing. Interim reports have not shown that enhanced tumor activity or enlarged antitumor spectrum are expected.
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PMID:[Preclinical and clinical evaluation of toxicity and antitumor activity of cisplatin analogues]. 265 26

Antitumor activity of a newly synthesized platinum complex, DWA2114R, by the serial administration was examined and compared with that of cis-diammine-1,1-cyclobutane dicarboxylato platinum (II) (CBDCA). In mice transplanted s.c. with tumor, the serial i.p. administration resulted in the increases of both maximal tolerated dose (MTD) and growth inhibitory ratio (GIR) of DWA2114R than single administration. Such increases in MTD and GIR were also shown by CBDCA, but the degree of these increases, such as the ratio of MTD or GIR by the serial administration compared to that at the single administration, was higher in DWA2114R than CBDCA. GIR of DWA2114R by the serial administration was higher than that of CBDCA at the doses to induce the same toxicity which was estimated by body weight loss. In addition, in the experiment using ascites tumor-bearing mice, better antitumor activity of DWA2114R was shown by the elongation of survival time. These results indicate that the cumulative toxicity of DWA2114R is lower than that of CBDCA, which causes the therapeutic advantages of DWA2114R in the serial administration.
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PMID:[Antitumor activity of a new platinum complex (R)-(-)-2-aminomethylpyrrolidine (1,1-cyclobutane dicarboxylato) platinum (II) (DWA2114R) by its serial administration]. 265 40

The prognosis of patients with squamous cell carcinoma (SQC) of the head and neck (H&N) depends on the primary site and anatomical extent of the disease. Recurrence rates after conventional surgery (S) and/or radiotherapy (RT) remain low for localized tumors, whereas in advanced loco-regional disease they occur in over 60% of all cases. Several combinations of treatment modalities have been attempted in order to improve local control in Stages III and IV. Unfortunately, the recurrence rate remains high with added morbidity when conventional surgery is combined with pre or post-operative radiotherapy. Induction chemotherapy (CT) with Cisplatinum and Bleomycin has resulted in severe toxicities when combined with radiotherapy. To evaluate the toxicity of Carboplatin (CBDCA), a second generation platinum analog, when given simultaneously with conventional doses of radiotherapy, 26 patients with Stage IV SQC of the head and neck were treated at the University of Maryland Medical Systems. There were 23 males and 3 females; median age was 59 years and median Karnofski performance status was 60. Twenty patients had received no prior therapy; six had surgical exploration and excision with measurable residual disease. Anatomically, six patients had tumors of the oral cavity, twelve in the pharynx, one in the nasopharynx, four in the larynx, one in the hypopharynx, one in the maxillary antrum, and one was an unknown primary. These patients were treated as out-patients with weekly injections of Carboplatin. The dose was escalated: two patients received 60 mg/M2, seven received 75 mg/M2, thirteen were treated with 100 mg/M2, and four with 400 mg/M2. The radiotherapy was given daily with conventional fractions of 180 cGy and total tumor doses of 60-75 Gy. Toxicities were mainly hematological with median nadirs decreasing with increasing doses of Carboplatin. Mucositis was seen in over 80% of the patients, but interestingly enough, it has never been more severe than that observed with radiotherapy alone. So far, there has not been any kidney, ear, or neurotoxicities. Of 25 evaluable patients, 19 (76%) responded with 13 (52%) showing complete response. The overall median survival time is 266+ days (324+ for responders and 179+ for non-responders). The follow-up is still short, 10-14 months, but 9 of 13 patients with complete response have not yet progressed.
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PMID:Carboplatin (CBDCA) and radiotherapy for stage IV carcinoma of the head and neck: a phase I-II study. 266 66

The efficiency and toxicity of Carboplatin, a derivate of cisplatin in clinical use since 1981, was investigated in combination with VP16 in 11 children with recurrent or refractory tumors. 10 patients received therapy as outpatients without hydration. 160 mg/m2/day of Carboplatin were administered days 1 to 3, or days 1 to 5 as one hour infusion, combined with VP16 100 mg/m2/day, days 1 to 3, or days 1 to 5 as one hour infusion. One patient received Carboplatin, 600 mg/m2, as 24 hrs. continuous infusion in combination with VM26, 150 mg/m2/day as one hour infusion, 8 hours after Carboplatin. 9 of the treated children had measurable disease. 3 of 9 patients achieved a tumor response of more than 50% (partial remission). 5 of 9 children showed tumor response of less than 50% (stable disease). 1 out of 9 patients had progressive disease. 8 of 9 patients reported improvement or disappearance of clinical symptoms after the first course. All patients had severe myelosuppression with different times to recover. The WBC nadir was 14 days after Carboplatin/VP16. The nadir platelet counts occurred 21 days after therapy with fast recovery. Non-hematological side effects were minimal.
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PMID:[Experiences with the combination carboplatin/VP 16 in the treatment of recurrent tumors in children]. 267 35

The biological basis of radiation damage modulation with platinum derivatives are reviewed. Cisplatin and Carboplatin are cytostatic agents used increasingly in the treatment of different human tumours. In vitro and in vivo studies have established the interest of the simultaneous combination of platinum compounds and radiation in tumor cells and neoplastic tissue, describing potentiation, sensitization, and inhibition of sublethal damage repair effects from radiation. Clinical trials have been recently activated in order to explore a possible benefit from the biological modulation with platinum compounds of radiotherapy. In the frame of developmental therapeutic protocols in modern oncology, this approach might explore a positive effect on the therapeutic index of radiotherapy for malignant tumors. The initial clinical results reported indicate that the available platinum derivatives used in human oncology behave as radiopotentiating and radiosensitizing agents.
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PMID:[Changes in radiation lesions using platinum derivatives. Biological bases and clinical experience]. 270 68


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