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

Experimental chemotherapy with cisplatin and carboplatin was performed against nine human tumor xenografts serially transplanted into nude mice. Tumors used for the experiment were seven gastric (St-4, St-15, St-40, H-111, SC-2-JCK, SC-6-JCK and Exp-4), one breast (MX-1) and one colon (Co-4) carcinomas. Cisplatin 9 mg/kg and carboplatin 100 mg/kg were administered intraperitoneally (ip). Carboplatin 25 mg/kg was also given ip 4 times every 4 days. The efficacy rates of cisplatin and carboplatin by bolus injection were 77.8% and 66.7% respectively with no statistically significant differences. However, carboplatin was found more effective when given by bolus. The antitumor spectra of both drugs were similar. From these results, these two platinum compounds seemed to be effective against human gastric carcinomas.
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PMID:[Antitumor activity of cisplatin and carboplatin against human tumor xenografts serially transplanted into nude mice--with special reference to gastric carcinomas]. 330 33

An in vitro assay, which evaluates drug effect on 3H-thymidine incorporation, was used to investigate the absolute and relative activities of cisplatin (DDP), carboplatin (CBDCA) and iproplatin (CHIP) on 317 specimens from untreated tumors, including breast and ovarian cancers and malignant melanomas. Similar activities were generally observed for DDP and CHIP, whereas CBDCA exhibited a lower, although not significantly different cytotoxicity on breast and ovarian cancers. The relative activities of Platinum analogues were analyzed on 239 two-way drug sensitivity comparisons. The overall agreement rates ranged from 80.2 to 83.9% for the different comparisons. High coresistance, from 61.1 to 93.8%, was observed for all the comparisons, regardless of the tumor type. Cosensitivity rates were poor for breast and ovarian cancers, from 0 to 37.5%, whereas for melanomas an association in sensitivity was observed in 80% of the cases.
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PMID:Absolute and relative activities of platinum-complexes on human tumors as evaluated by an antimetabolic in vitro assay. 331 80

Carboplatin is one of a series of cisplatin analogs now undergoing clinical investigation. Phase I and II trials in adults demonstrate activity in a number of human cancers and less toxicity than might be expected with the parent compound. This phase I trial was undertaken to establish the maximum tolerated dose and the recommended phase II dose in children treated by a 1-hour iv infusion every 4 weeks. Twenty-nine patients with recurrent or progressive tumor were entered in this study at the Children's Hospital of Los Angeles and Children's Memorial Hospital in Chicago between April 12, 1983, and November 27, 1984. Beginning with a dose of 350 mg/m2 (about 80% of the adult phase II dose), we escalated the dose in groups of patients to 670 mg/m2; dose-limiting myelosuppression was encountered at this dose. Fifty-seven infusions are at least partially evaluable for toxicity. Asymptomatic hypomagnesemia, hypocalcemia, and ototoxicity were observed infrequently, and nausea and vomiting were mild. One patient with a mixed glioma of the posterior fossa achieved a good partial response lasting 9 months. Stable disease for greater than or equal to 6 months was observed in three patients: one each with ependymoma, brain stem glioma, and spinal cord astrocytoma. The recommended pediatric phase II dose is 560 mg/m2 given as a 1-hour iv infusion every 4 weeks.
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PMID:Pediatric phase I trial of carboplatin: a Childrens Cancer Study Group report. 331 95

We compared the antitumor activity of cis-diamminedichloroplatinum(II) (cisplatin; CDDP) with three CDDP analogues: cis-diammine-1,1-cyclobutanedicarboxylateplatinum(II) (CBDCA), N-methyliminodiacetato-1,2-diamino(cyclohexane)platinum(II) (MIDP), and N-(2-hydroxyethyl)-iminodiacetato-1,2-diamino(cyclohexane)platinum (II) (HIDP). Fresh human tumor samples in the adhesive tumor culture system were utilized for this comparison. The equitoxic concentrations of all four drugs were derived based on their inhibitory activity against human bone marrow samples. For these normalized concentrations, CDDP proved to have a higher cytotoxic activity than its analogues. CBDCA's in vitro activity had a significant correlation with CDDP activity (r = 0.67) in vitro. However, the structurally similar substances MIDP and HIDP demonstrated a much greater degree of association (r = 0.90). Our data suggest that CBDCA, HIDP, and MIDP have overall less activity than CDDP when tested at equitoxic in vitro concentrations. Close association between CDDP and CBDCA also reflects known clinical experience with these two drugs, suggesting the method of comparison used here is probably appropriate. These conclusions, however, must be validated by clinical trials.
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PMID:Antitumor activity against human tumor samples of cis-diamminedichloroplatinum(II) and analogues at equivalent in vitro myelotoxic concentrations. 336 98

The kinetics of intratumoral uptake of cisplatin, carboplatin (CBDCA) and TNO-6 were studied in vitro in fragments of tumors of the head and neck maintained in culture medium under conditions simulating therapeutic conditions of chemo-embolization. Cisplatin and TNO-6 are more rapidly taken up than CBDCA (carboplatin). With each of these compounds, after 24 hours a fraction of the platinum taken up is not irreversibly bound to the tissue. The rate of uptake and the proportion of platinum irreversibly bound depends a great deal on the tumor under study. The characteristics of the diffusion indicate that TNO-6 is better used with chemo-embolization than with systemic injection. The opposite finding is seen with carboplatin. Cisplatin appears to to be about equally well-suited for either method of injection.
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PMID:Uptake of platinum compounds in human tumors. In vitro study. 353 36

Six patients with histologically proven stage III-IV ovarian carcinoma received carboplatin (CBDCA) (150 mg/m2) plus cyclophosphamide (1000 mg/m2) monthly for 1 year unless disease progressed earlier. Six other patients received CBDCA (225 mg/m2) with the same cyclophosphamide dose monthly. Continued treatment with the higher CBDCA dose was not tolerable because of myelosuppression, but no other dose-limiting toxic effect was observed. Complete tumor regression was proven at secondary laparotomy in six of the 12 patients, and five of these remain disease-free from 26+ to 28+ months after beginning chemotherapy.
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PMID:Pilot study of cyclophosphamide plus carboplatin in advanced ovarian carcinoma. 354 10

The chemotherapeutic effects of CDDP, CBDCA and CHIP on human ovarian cancers heterotransplanted into nude mice (mucinous cystadenocarcinoma OVA-1, poorly differentiated adenocarcinoma OVA-2, endometrioid adenocarcinoma OVA-3, serous cystadenocarcinoma OVA-4, and three yolk sac tumors YST-1, YST-2, YST-3) were examined. OVA-1 did not respond to CDDP, although it responded well to CBDCA and CHIP. OVA-2 responded well to all these platinum analogs. OVA-3 responded well to CDDP, but did not respond to CBDCA or CHIP. OVA-4 responded well to CDDP and CBDCA, but did not respond to CHIP. Tumors YST-2 and YST-3 exhibited broadly comparable sensitivity to CDDP and the two other analogs, and YST-1 was substantially more sensitive to CDDP than to CBDCA or CHIP. The results indicated the necessity of selection of platinum analogs according to the histological types of tumor for the effective treatment of ovarian cancer.
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PMID:[Antitumor activity of platinum analogs against human ovarian tumors heterotransplanted into nude mice]. 354 96

Carboplatin has been developed for clinical trials as a less nephrotoxic, less emetogenic analog of cisplatin. In preclinical tumor models it was less potent than the parent compound on a molar basis, but reduced toxicity allowed comparable antitumor doses to be given. In phase I studies its dose-limiting toxicities were reversible myelosuppression, especially thrombocytopenia. Leucopenia and anemia occurred to a lesser degree. Other reported toxicities included nausea, vomiting, malaise, myalgia, arthralgia, ototoxicity, hypomagnesemia, and proteinuria. Nausea and vomiting occurred frequently, but was much less severe than that observed with cisplatin. The incidence of serum creatinine elevations was low. The increase was usually reversible and occurred only in association with administration of aminoglycosides, or abnormal pretreatment renal function. Recommended phase II doses by schedule are: bolus every 4 weeks, 400-500 mg/m2 (560 mg/m2 in children); 24 hour continuous infusion every 4 weeks, 320-400 mg/m2; weekly bolus for 4 consecutive weeks with 2 weeks rest, 100-125 mg/m2 (175 mg/m2 in children); bolus for 5 consecutive days every 4 weeks, 77-95 mg/m2. Objective responses were observed during these phase I studies in adult patients (head and neck, breast, renal carcinomas) and children (osteosarcoma, brain stem lesions). In addition to phase II evaluations in all major tumor types, plans for phase III studies in selected tumors are underway.
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PMID:Results of NCI-sponsored phase I trials with carboplatin. 391 Feb 21

Since the discovery of the antitumor activity of cis-dichlorodiammine platinum (II) in various tumor systems by B. Rosenberg in 1969, many Pt complexes have been prepared to ameliolate DDP. It has been known to have severe nephrotoxicity, nausea and vomiting, as well as ototoxicity. However, DDP has a wide spectrum of antitumor activity, and it is specifically active against cancers in bladder, testis, ovary and, head and neck. To attenuate such toxicities, hydration prior to DDP administration and/or application of diuretics, as well as combination therapy with other antitumor agents have been developed. Various studies indicated that the nephrotoxicity was attenuated by changing carrier ligands and leaving groups. Toxicity to be removed so far is myelosuppression and vomiting. Another problem is the cross-resistance of DDP. Against L1210/DDP, amine, ethylenediamine, o-phenylenediamine and 1,2-cyclopentanediamine Pt complexes showed cross-resistance, while dach and 1,2-cycloheptanediamine Pt complexes showed no cross-resistance. In this review, the author discusses mainly preparation of the Pt complex of the 2nd generation, being now in the clinical trials and my approach to the development of the antitumor Pt complexes in my laboratory. Pt complexes being now in the advanced studies are: CBDCA, CHIP, DACCP, PYPl PHIC, TNO-6 and l-OHP. New Pt complexes are still deviced continuously. The capability of synthesizing Pt complexes which are characteristically effective against the slow-growing solid tumors, from the standpoint of the coordination chemist.
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PMID:[Development of antitumor platinum complexes]. 636 50

The effect of various doses (75-300 mg/kg b.w.) of carboplatin on the induction of micronuclei in Ehrlich ascites tumor (EAT) cells was studied. Carboplatin treatment resulted in a dose-dependent increase in the frequency of micronucleated EAT cells. Carboplatin treatment also decreased the mitotic index. The dose-effect curves were linear-quadratic for all the parameters studied. The maximal effect of the drug was obtained in all the treatments after 48 h.
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PMID:Carboplatin treatment induces dose-dependent increases in the frequency of micronuclei in Ehrlich ascites tumor cells. 751 4


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