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  • 1
    Electronic Resource
    Electronic Resource
    In vitro antitumor activity of mitomycin C derivative (RM-49) and new anticancer antibiotics (FK973) against lung cancer cell lines determined by tetrazolium dye (MTT) assay (1988)
    Springer
    Cancer chemotherapy and pharmacology 22 (1988), S. 246-250 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Seven small- (SCLC) and four non-small-cell (NSCLC) lung cancer cell lines were used to examine the in vitro cytotoxicity of cytotoxic drugs such as (1aS-(1aα,8β,8aα,8bα))-8-((aminocarbonyl)oxy)methyl-4,8a-dimethoxy-1,1a,2,8,8a,8b-hexahydro-7-hydroxy-5-methyl-6-nitrosoazirino(2′,3′: 3,4)-pyrrolo-(1,2-a)indole (RM-49) and 11-acetyl-8-carboxymethyl-4-formyl-14oxa-1, 11-diazetetracyclo(7.4.1.02,7,010,12)tetradeca-2-4-6-trien-6,9-diyl-diacetate (FK973). In vitro cytotoxicities of RM-49 and FK973 were compared with those of mitomycin C (MMC), cisplatin (CDDP), carboplatin (CBDCA), etoposide (VP16), adriamycin (ADM) and vindesin (VDS). Drug sensitivity was determined using a tetrazolium (MTT)-based assay. Average IC50 values of these two drugs were not statistically different compared with that of MMC, although FK973 showed strong antitumor activity against SCLC cell lines such as LT3, N857, and H69 at the same concentration. The predicted peak plasma concentration (predicted PPC) calculated by the formula proposed by Scheithauer, log (predicted PPC) =-0.788+(0.755×log(LD50)), and relative antitumor activity, RAA (PPC/IC50), of RM-49 were higher than those of other drugs such as MMC, CDDP, CBDCA, and ADM against SCLC cell lines (P≦0.05), and those of FK973 were also higher than those of other drugs such as MMC, CDDP, CBDCA, and ADM against SCLC cell lines (P≦0.05). Based on these promising in vitro studies, the clinical trials of RM-49 and FK973 were warranted.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00273419
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  • 2
    Electronic Resource
    Electronic Resource
    Comparative study of the antitumor effect of two types of murine recombinant interferons, (β) and (γ), against B16-F10 melanoma (1988)
    Springer
    Cancer immunology immunotherapy 26 (1988), S. 109-113 
    Details
    ISSN: 1432-0851
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A comparative study of the antitumor effect of murine recombinant interferon(β) 〈Mu-rIFN(β)〉 and murine recombinant interferon(γ) 〈Mu-rIFN(γ)〉 on B16-F10 melanoma was conducted. Administration of Mu-rIFN(γ) i.p. into C57BL/6 mice on days 1 to 7 produced a higher suppressive effect than Mu-rIFN(β) both on the growth of s.c. implanted tumor and on the formation of artificial pulmonary metastasis. Pharmacokinetic study of Mu-rIFN(γ) demonstrated that high plasma levels were retained for a long time. In clonogenic assay, Mu-rIFN(γ) at 1000 units/ml showed about 80% inhibition of colonies of B16-F10 melanoma. However, Mu-rIFN(β) hardly inhibited the colonies, even at 1000 units/ml. Augmentation of natural killer (NK) cytotoxicity was much greater with Mu-rIFN(β) than Mu-rIFN(γ), whereas Mu-rIFN(γ) enhanced the cytotoxicity of peritoneal macrophages more strongly than Mu-rIFN(β). Injection of Mu-rIFN(γ) i.p. 1 day before tumor challenge also inhibited the formation of pulmonary metastasis of B16-F10 melanoma. However, pretreatment of mice with carrageenan significantly suppressed the inhibitory effect of Mu-rIFN(γ). From these results, it is suggested that the inhibitory effect of Mu-rIFN(γ) on the tumor growth and metastases of B16-F10 melanoma is mediated partly by direct antitumor effect and partly by the activation of macrophages, and that the augmentation of NK activity contributes mainly to the antitumor effect of Mu-rIFN(β).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00205602
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  • 3
    Electronic Resource
    Electronic Resource
    Prediction of the antitumor activity of new platinum analogs based on their ex vivo pharmacodynamics as determined by bioassay (1991)
    Springer
    Cancer chemotherapy and pharmacology 27 (1991), S. 263-270 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We report the predictive model for the clinical response of new platinum analogs against lung cancer by a bioassay using human lung-cancer cell lines including small-cell (SCLC) and non-small-cell lung cancer (NSCLC). Exponentially growing cells of six different SCLC and sic NSCLC lines were exposed to different concentrations of the three platinum compounds, cisplatin, carboplatin, and 254-S in a double-agar colony-forming cell assay. The concentrations inhibiting 50% of colony formation (IC50 value) for cisplatin, carboplatin and 254-S in SCLC cell lines were significantly lower than those in NSCLC cell lines. A total of 15 patients entered the pharmacological study. In all, 80 mg/m2 cisplatin, 450 mg/m2 carboplatin, and 100 mg/m2 254-S were each given to five patients by intravenous drip infusion. Bioassay as well as chemical assay was achieved by clonogenic techniques using NCI-H-69 (SCLC cell line) and PC-9 (NSCLC cell line) as target cells. Biological comparison of antitumor activity was performed on the basis of the antitumor activity of patients' plasma using the antitumor index (ATI), which was defined as the area under the percentage of colony suppression versus time curve obtained by bioassay and calculated by the trapezoidal rule. When NCI-H-69 and PC-9 were used as target cells for bioassay, colony-inhibitory activity was revealed by the ATIs. The ATIs obtained by bioassay showed better correlation than the AUCs obtained by chemical assay with the clinical response for cisplatin and carboplatin against SCLC and NSCLC, according to the following equation: [Reported Response (%)]=11.5668+0.0014×[ATI] (r=0.97). The response rates for 254-S against SCLC and NSCLC were predicted by this formula to be 40%–65% and 14%–16%, respectively. 254-S is prospectively suspected of having the same, if not more, activity then carboplatin against SCLC and of having almost the same activity as cisplatin against NSCLC.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00685110
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  • 4
    Electronic Resource
    Electronic Resource
    A prognostic-factor risk index in advanced non-small-cell lung cancer treated with cisplatin-containing combination chemotherapy (1992)
    Springer
    Cancer chemotherapy and pharmacology 30 (1992), S. 1-6 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Prognostic factors for response and survival were retrospectively evaluated in 192 previously untreated patients with advanced non-small-cell lung cancer (NSCLC) who had received either vindesine plus cisplatin or mitomycin plus vindesine plus cisplatin as initial treatment. Univariate analysis demonstrated that squamous-cell histology, early stage, and a small number of metastatic sites were favorable prognostic factors for response to chemotherapy. Multivariate analysis using Cox's proportional hazard model indicated that the number of metastatic sites was the only significant pretreatment factor for response (P=0.0005). Multivariate regression analysis revealed that the number of metastatic sites (P=0.0002), sex (P=0.0009), serum albumen levels (P=0.0018), performance status (P=0.0026) and lactic dehydrogenase values (P=0.0026) contributed independently to survival. On the basis of these five prognostic factors, a prognostic index for survival was used to define three prognostic groupings (good, intermediate, and poor) for survival (median survival, 16.5 vs 9.4 vs 4.6 months;P=0.0001). This particular regression model should aid in the design and analysis of new treatment strategies and may be useful for indirect comparisons of different studies carried out in similar patient populations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00686477
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  • 5
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of (glycolato-0,0′)-diammine platinum (II), a new platinum derivative, in comparison with cisplatin and carboplatin (1989)
    Springer
    Cancer chemotherapy and pharmacology 23 (1989), S. 243-246 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The pharmacokinetics of (glycolato-0,0′)-diammine platinum (II) (254-S; NSC 375101D), one of the new platinum analogues, was examined in a phase I study of this drug and compared with that of cisplatin and carboplatin. All drugs were given in short-term (30-min) i.v. drip infusions; the doses of 254-S, cisplatin, and carboplatin were 100, 80, and 450 mg/m2, respectively. Platinum concentrations in whole plasma, plasma ultrafiltrate, and urine were determined by atomic absorption spectrometry. After the infusion, the plasma concentration of total platinum for the three agents decayed biphasically. Ultrafilterable platinum in plasma decreased in a biexponential mode after infusions of 254-S and carboplatin, whereas the free platinum of cisplatin showed a monoexponential disappearance. The peak plasma concentrations and AUC for free platinum were 5.31 μg/ml and 959 μg/min per ml for 254-S, 3.09 μg/ml and 208 μg/min per ml for cisplatin, and 19.90 μg/ml and 3446 μg/min per ml for carboplatin, respectively. The mean ratio of plasma ultrafilterable platinum to total platinum were calculated, and the results showed that the protein-binding abilities of 254-S and carboplatin were almost identical. More than 50% of the 254-S was excreted in the urine within the first 480 min after its administration. Thrombocytopenia was reported as a dose-limiting toxicity for both 254-S and carboplatin. This similarity in side effects may mainly be due to the comparable pharmacokinetic behavior of these two platinum compounds.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00451649
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  • 6
    Electronic Resource
    Electronic Resource
    In vitro enhancement of fluoropyrimidine-induced cytotoxicity by leucovorin in colorectal and gastric carcinoma cell lines but not in non-small-cell lung carcinoma cell lines (1992)
    Springer
    Cancer chemotherapy and pharmacology 30 (1992), S. 417-422 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Leucovorin (LV) increases the cytotoxic effect of fluorouracil (FUra) and 5-fluoro-2′-deoxyuridine (FdUrd) by enhancing the formation of the fluorodeoxyuridine monophosphate (FdUMP) thymidylate synthase (TS) 5,10-methylenetetrahydrofolate (mTHF) ternary complex. To study the difference in the efficacy of this combination against different tumors, we compared the effect of LV (20 μm) on the cytotoxicity of FUra, FdUrd, and 5-fluorouridine (FUrd) in vitro against cell lines of five colorectal carcinomas (CC), five gastric carcinomas (GC), and four non-small-cell lung carcinomas (NSCLC) using the colony-forming assay. At the concentration used in the experiments, LV alone failed to inhibit colony formation in any of the cell lines tested. The NSCLC cell lines were more resistant to FdUrd than were the CC and GC lines. LV modulated the cytotoxicity of FdUrd in all five CC lines and in three of the five GC lines but failed to do so in any of the NSCLC lines. In addition, following 20 h treatment with 1 μm [3H]-FdUrd, formation of the FdUMP/TS/mTHF ternary complex was enhanced by LV in the LV-sensitized CC and GC cell lines but not in the LV-refractory NSCLC lines. These in vitro data corresponded well to the results of clinical trials. Therefore, the colony-forming assay may be useful for the identification of the sensitivity of tumors according to phenotype.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00685591
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  • 7
    Electronic Resource
    Electronic Resource
    7-Ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxy camptothecin: mechanism of resistance and clinical trials (1994)
    Springer
    Cancer chemotherapy and pharmacology 34 (1994), S. S112 
    Details
    ISSN: 1432-0843
    Keywords: CPT-11 ; Topoisomerase I ; Dose-limiting toxicity ; Resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The camptothecin derivative 7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxy camptothecin (CPT-11) has attracted the attention of clinicians because of its high antitumor activity against refractory solid cancers. We established two CPT-11-resistant cell lines, a non-small-cell lung-cancer cell line (PC-7/CPT-11) from the parental PC-7 line and an ovarian cancer cell line (HAC-2/CPT-11) from the parental HAC-2 line. The mechanisms of resistance to CPT-11 in PC-7/CPT-11 cells were reduced conversion of CPT-11 to its active metabolite SN-38 and point mutation of topoisomerase I. Those in HAC-2/CPT-11 cells were reduction of topoisomerase I activity and decreased sensitivity of topoisomerase to topoisomerase I inhibitors. No point mutation of the topoisomerase was observed in HAC-2/CPT-11 cells. We conducted two phase I trials using CPT-11 in combination with other anticancer agents. One was a phase I trial of CPT-11 and cisplatin given with a fixed dose of vindesine to patients with advanced non-small-cell lung-cancer and the other was a phase I study on a topoisomerase-targeting combination of CPT-11 and etoposide (VP-16) in patients with various malignant solid tumors. The results of the first trial indicated that the recommended dose of CPT-11 for phase II studies was 80 mg/m2 combined with 3 mg/m2 vindesine on days 1 and 8 and 60 mg/m2 cisplatin on day 1. In the second trial, the recommended dose of CPT-11/VP-16 given with recombinant granulocyte colony-stimulating factor (on days 4–17) was found to be 60/60 mg/m2 In both trials, diarrhea and granulocytopenia were considered to be dose-limiting toxicities.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00684874
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  • 8
    Electronic Resource
    Electronic Resource
    The influence of ageing on cisplatin pharmacokinetics in lung cancer patients with normal organ function (1995)
    Springer
    Cancer chemotherapy and pharmacology 36 (1995), S. 102-106 
    Details
    ISSN: 1432-0843
    Keywords: Cisplatin ; Ageing ; Pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study was performed to identify any relationship between age and cisplatin (CDDP) pharmacokinetics in lung cancer patients. CDDP was given at a dose of 80 mg/m2 by 1-h intravenous infusion to 23 lung cancer patients. All patients had normal renal, hepatic, and bone marrow functions. We measured ultrafilterable platinum (U-Pt) and total plasma platinum (T-Pt) using atomic absorption spectrometry. There was significant correlation between the age of the patients and U-Pt pharmacokinetic parameters such as the area under the plasma concentration versus time curve (AUC), total clearance (Cl), and peak plasma concentration (Cmax) as well as the AUC of T-Pt (P〈0.05). We performed univariate regression analysis to examine the influence of factors aside from age on the AUC of U-Pt and T-Pt. Creatinine and GPT levels were significantly related to the AUC of U-Pt, and creatinine clearance and creatinine concentrations were significantly related to the AUC of T-Pt. Therefore, stepwise multiple-regression models for the AUC of U-Pt and T-Pt were developed to assess an age effect. Age was consistently an independent and significant predictor of the AUC of U-Pt and T-Pt.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00689192
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  • 9
    Electronic Resource
    Electronic Resource
    The influence of ageing on cisplatin pharmacokinetics in lung cancer patients with normal organ function (1995)
    Springer
    Cancer chemotherapy and pharmacology 36 (1995), S. 102-106 
    Details
    ISSN: 1432-0843
    Keywords: Key words: Cisplatin ; Ageing ; Pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  This study was performed to identify any relationship between age and cisplatin (CDDP) pharmacokinetics in lung cancer patients. CDDP was given at a dose of 80 mg/m2 by 1-h intravenous infusion to 23 lung cancer patients. All patients had normal renal, hepatic, and bone marrow functions. We measured ultrafilterable platinum (U-Pt) and total plasma platinum (T-Pt) using atomic absorption spectrometry. There was significant correlation between the age of the patients and U-Pt pharmacokinetic parameters such as the area under the plasma concentration versus time curve (AUC), total clearance (Cl), and peak plasma concentration (Cmax) as well as the AUC of T-Pt (P〈0.05). We performed univariate regression analysis to examine the influence of factors aside from age on the AUC of U-Pt and T-Pt. Creatinine and GPT levels were significantly related to the AUC of U-Pt, and creatinine clearance and creatinine concentrations were significantly related to the AUC of T-Pt. Therefore, stepwise multiple-regression models for the AUC of U-Pt and T-Pt were developed to assess an age effect. Age was consistently an independent and significant predictor of the AUC of U-Pt and T-Pt.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00689192
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  • 10
    Electronic Resource
    Electronic Resource
    Progress in preclinical and clinical studies for the development of new anticancer drugs in Japan, with emphasis on taxanes (1996)
    Springer
    Cancer chemotherapy and pharmacology 38 (1996), S. S11 
    Details
    ISSN: 1432-0843
    Keywords: Key words Taxane ; Anticancer drugs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002800051030
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