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  • 1
    Electronic Resource
    Electronic Resource
    IgM response and resistance to ascites tumor growth (1987)
    Springer
    Cancer immunology immunotherapy 25 (1987), S. 87-92 
    Details
    ISSN: 1432-0851
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Antibody response and protection against Ehrlich ascites tumor (EAT) was studied in eight EAT-immunized strains of mice (AL/N, BALB/C, C57BL/6J, F1(C57BL/6×BALB/C), C57BL/10J, B10.BR, CBA/Ca, SW). The results showed a close association between IgM response and resistance to subsequent tumor challenge. Thus, protection was only achieved in those animals giving a measurable IgM response against EAT cell surface antigens, i.e., all inbred strains of mice tested, except CBA/Ca, and some outbred SW mice. The lack of IgM response to these antigens in CBA/Ca was not linked to the strain H-2 haplotype. Resistance could be passively transferred to nonimmunized mice by means of serum, or purified IgM, from protected immune animals. Moreover, complement depletion by cobra venom factor treatment did not modify the protection afforded to those mice. IgM reactivity to EAT cells was completely abolished by previous cell trypsinization. Trypsin removed but did not destroy the antigen(s) recognized by the IgM, since all its activity could be absorbed with the supernatant of the EAT cell trypsinization. Absorption assays with this supernatant treated with different agents, showed that lipids, simple peptides and nucleic acids were not important components of the antigenic determinants. On the contrary, its susceptibility to β-galactosidase and particularly to a mild periodate oxidation, suggested that determinants recognized by the IgM against the EAT cell surface are carbohydrate in nature.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00199946
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  • 2
    Electronic Resource
    Electronic Resource
    Alteration of dacarbazine pharmacokinetics after interleukin-2 administration in melanoma patients (1990)
    Springer
    Cancer chemotherapy and pharmacology 27 (1990), S. 157-160 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In an effort to improve the treatment of metastatic malignant melanoma, we evaluated the sequential administration of the chemotherapeutic agent dacarbazine (DTIC) and the biological response modifier interleukin-2 (rIL-2) in a phase I–II study. Since the combination of biological response modifiers and chemotherapeutic agents could alter drug disposition, we evaluated the pharmacokinetics of DTIC and its major metabolite, 5-aminoimidazole 4-carboxamide (AIC), before and after rIL-2 administration. DTIC (1 g/m2, 24-h i.v. infusion) was given on day 1 and rIL-2 (2–4 million Cetus units/m2, 30-min i.v. injection), on days 15–19 and 22–26 of each course of therapy. The second DTIC dose was given on day 29, i.e., 3 days after the last rIL-2 administration. DTIC and AIC were assayed by reversed-phase HPLC. DTIC plasma levels showed a significant decrease after rIL-2 administration as compared with DTIC values obtained in the same patients before rIL-2 administration. DTIC area under the curve (AUC) values obtained after rIL-2 were lower than those obtained on day 1 before rIL-2 administration (P=0.02). After rIL-2, the total body clearance (ClT) was increased (P=0.04), as was the volume of distribution at steady state (Vss;P=0.02). The decrease in AUC after rIL-2 administration became more pronounced as the rIL-2 dose was increased (P=0.03). No significant difference was detected in the elimination phase of DTIC when halflives obtained before and after rIL-2 administration were compared; the mean half-lives were 0.7 and 2.8 h for the α- and β-phases, respectively. The model-independent mean residence time was 3.4 h. The plasma AUC for the metabolite AIC did not charge after rIL-2 administration. AIC biphasic plasma elimination was also similar after rIL-2 administration, with α- and β-half-lives of 0.7 and 11.4 h, respectively. Urinary excretion of DTIC and AIC did not differ after rIL-2 administration; the overall DTIC excretion was 39% of the dose over 48 h, and AIC urinary excretion was 25% of the DTIC dose. The observed decrease in the DTIC plasma AUC after rIL-2 administration appears to be due to an increase in the volume of distribution, since other factors such as half-lives, urinary excretion, and metabolism were not significantly altered. The clinical consequences of the rIL-2-DTIC interaction remain difficult to assess based on presently available data, but this drug interaction should be taken into consideration in the development of future chemo-immunotherapy regimens that include high-dose rIL-2.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00689102
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  • 3
    Electronic Resource
    Electronic Resource
    Effect of thymidine on the toxicity and antitumor activity of Cis-diamminedichloroplatinum (II) (1984)
    Springer
    Cancer chemotherapy and pharmacology 13 (1984), S. 27-30 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of thymidine (TdR) on the preclinical toxicity of cis-diamminedichloroplatinum (II) (DDP) was investigated in the BDF1 mouse and the Sprague-Dawley rat. The effect of TdR on the antitumor activity of DDP was investigated using the ascites P388 murine leukemia model. TdR at 500 mg/kg consistently decreased the recovery of body weight after DDP treatment IP, but did not affect the lethal toxicity of DDP to non-tumor-bearing mice or those with the P388 murine leukemia. This effect was greatest when TdR was injected 30 min prior to DDP and at higher doses of DDP. A500-mg/kg dose of TdR did not affect the antitumor activity of DDP 5 mg/kg administered on days 1, 5, and 9. Treatment of rats with TdR 500 mg/kg according to various schedules of timing relative to a 5-mg/kg dose of DDP did not consistently affect the DDP-related loss in body weight or nephrotoxicity at day 3. Pretreatment of mice with TdR 1,500 mg/kg 30 min prior to DDP 5 mg/kg (every 4 daysx3) resulted in a slower recovery of body weight, which became more pronounced with increasing doses of DDP. Pretreatment of ascites P388-bearing mice with TdR 1,500 mg/kg increased the number of early deaths when mice were treated with DDP 5 mg/kg (days 1, 5, and 9). These data suggest that the cytotoxicity of DDP is increased by TdR only at higher doses of either drug, but that the antitumor activity against P388 murine leukemia is not affected.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00401442
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  • 4
    Electronic Resource
    Electronic Resource
    Clinical, toxicological, and pharmacological studies of combination chemotherapy of adenocarcinoma with Adriamycin and Baker's Antifolate (1978)
    Springer
    Cancer chemotherapy and pharmacology 1 (1978), S. 139-144 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Ten patients with disseminated adenocarcinoma were treated with combination chemotherapy employing Adriamycin and Baker's Antifolate (BAF). There were seven patients with lung adenocarcinoma, two of whom achieved partial remission while the remaining five had their disease stabilized. Drug toxicity to the bone marrow, gastrointestinal mucosa, and skin was dose-limiting and was greater than the known toxicities of the individual drugs. Pharmacological studies of both drugs were performed on five patients to determine whether abnormal pharmacokinetics could explain this collateral toxicity. Adriamycin plasma concentrations and disappearance seemed to be unaffected by BAF. However, BAF levels were prolonged, apparently due to an Adriamycin effect on the plasma elimination of BAF, resulting in a prolonged exposure of sensitive tissues and organs to BAF. Consequently, when BAF and Adriamycin are used in combination, appropriate dose and schedule changes must be made to avoid any potentially serious side effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00253114
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  • 5
    Electronic Resource
    Electronic Resource
    Phase I trial of Adozelesin using the treatment schedule of daily × 5 every 3 weeks (1995)
    Springer
    Investigational new drugs 13 (1995), S. 321-326 
    Details
    ISSN: 1573-0646
    Keywords: daily × 5 Adozelesin Phase I
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary CC-1065 is a unique alkylating agent that preferentially binds in the minor groove of double-stranded DNA at adenine-thymine-rich sites. Although it has broad antitumor activity in preclinical models its development was discontinued because of deaths observed during preclinical toxicology studies. Adozelesin is a potent synthetic analog that was chosen for clinical development because it had a similar preclinical antitumor spectrum, but did not produce deaths similar to CC-1065 at therapeutic doses. Phase I evaluations using a variety of Adozelesin treatment schedules have been conducted. This report describes our experience using a multiple dose treatment schedule. Endpoints including antitumor response, maximum tolerated dose, dose limiting toxicity as well as other toxicities and the recommended Phase II starting dose were determined. Adozelesin was given as a 10 minute IV infusion for 5 consecutive days every 21 days or upon recovery from toxicity. The dose range evaluated was 6–30 mcg/m2/day. All patients had refractory solid tumors and had received prior cytotoxic treatment. Thirty-three patients (22 men: 11 women) were entered onto the study and 87 courses were initiated. Dose limiting toxicity was cumulative myelosuppression (leucopenia, thrombocytopenia). The maximum tolerated dose was 30 mcg/m2/day. The only other significant toxicity was an anaphylactoid syndrome that occurred in 2 patients. A partial response was observed in a patient with refractory soft tissue sarcoma. The recommended Phase II starting dose of Adozelesin using a 10 minute IV infusion for 5 consecutive days is 25 mcg/m2/day to be repeated every 4–6 weeks to allow recovery from myelotoxicity, based on our experience. Additional Phase I and II studies with Adozelesin are recommended.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00873138
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  • 6
    Electronic Resource
    Electronic Resource
    Role of elective brain irradiation during combined chemoradiotherapy for limited disease non-small cell lung cancer (1984)
    Springer
    Journal of neuro-oncology 2 (1984), S. 253-259 
    Details
    ISSN: 1573-7373
    Keywords: brain irradiation ; lung cancer ; CNS metastasis ; chemotherapy-lung cancer ; radiotherapy-lung cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We have studied the clinical impact of elective brain irradiation (EBI) in patients with locally advanced, non-small cell lung cancer (LA-NSC). All patients received combination chemotherapy (cyclophosphamide +doxorubicin (Adriamycin) + cisplatin = CAP) or CAP plus radiotherapy as the initial treatment for their active tumor or as an adjuvant therapy. Of 97 evaluable patients, 46 were randomized to receive EBI (3 000 rad in 10 fractions given over two weeks). The characteristics of both groups were comparable by sex, age, performance status, pretherapy weight loss, histologic cell type, clinical staging, and type of prior therapy. EBI significantly decreased the incidence of central nervous system (CNS) metastasis in the treated group compared to the control group (4% vs 27%, p =.002). CNS involvement occurred in the treated group after failure at other sites whereas 12 of 14 control patients had CNS metastases as the first site of relapse. EBI decreased the incidence of CNS metastasis in all prognostic categories. Using multivariate analysis, the beneficial effect was shown to be significant in females, patients with good performance status, weight loss less than 6%, squamous cell histology, state III disease or no prior therapy. EBI significantly increased CNS metastasis-free interval with a beneficial effect that was significant in males, patients with weight loss less than 6%, squamous cell histology or responders. Although no survival benefit was observed for the treated group because of the adverse effect from other relapses, EBI will become more important as better treatment programs are developed. Our study, as well as others, revealed the high incidence of CNS metastasis in LA-NSC patients with no other evidence of disease. EBI should be considered as another adjuvant treatment along with other therapies in this group of patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00253278
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  • 7
    Electronic Resource
    Electronic Resource
    Phase II study of deoxydoxorubicin in previously untreated metastatic breast cancer (1990)
    Springer
    Breast cancer research and treatment 17 (1990), S. 139-143 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; chemotherapy ; deoxydoxorubicin ; phase II trial
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary With the objective of identifying new chemotherapeutic agents active against breast cancer, we administered the phase II agent deoxydoxorubicin (DxDx) to 25 patients who had received no prior chemotherapy for their metastatic breast cancer. A dose of 30–35 mg/M2 given at 3 week intervals resulted in a response rate of 12%. The patients were subsequently treated with a combination of 5-fluorouracil, methotrexate, vincristine, cyclophosphamide, and prednisone. A response rate of 38% was achieved with this combination as second line therapy. Toxicity of DxDx was predominately hematopoietic. One patient developed congestive heart failure. Median survival from onset of treatment with DxDx was 39 weeks. DxDx appears to be minimally active against metastatic breast cancer. Whether the administration of phase II agents as first line therapy offers an avantage in the overall management of metastatic cancer, needs further evaluation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01806294
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  • 8
    Electronic Resource
    Electronic Resource
    Difluorodeoxycytidine (dFdC) — gemcitabine: A phase I study (1992)
    Springer
    Investigational new drugs 10 (1992), S. 165-170 
    Details
    ISSN: 1573-0646
    Keywords: gemcitabine ; difluorodeoxycytidine ; phase I study
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Difluorodeoxycytidine (dFdC) demonstrated broad spectrum activity in preclinical models. A phase 1 study utilizing twice weekly injections was conducted in 50 eligible and evaluable patients. Twenty-nine patients received drug by 30 minute infusion at doses of 5–90 mg/m2 and 22, by 5 minute bolus at 30–150 mg/m2. The primary dose limiting toxicities were marrow suppression and flu-like symptomatology. Thrombocytopenia was dose limiting at 75 mg/m2 on the infusion schedule and 150 mg/m2 on the 5 minute schedule. Flu-like symptoms with fever, rigors and malaise occurred the day of injection in many patients. One patient with renal cell carcinoma attained a partial response. Evaluation of the drug's efficacy and schedule dependency continue.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00877241
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