Recent results with clinically used antineoplastic drugs and drug combinations in vivo

Our plain-English summary of Recent results with clinically used antineoplastic drugs and drug combinations in vivo, by W. Arnold, S. Tanneberger, C. Nowak, et al (Oncology, 1980).

The study

• Authors: W. Arnold, S. Tanneberger, C. Nowak, H. Naundorf
• Journal: Oncology
• Published: 1980;37 Suppl 1:34-41
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Using four mouse tumor systems--leukemia L1210, i.m. mammary carcinoma 1142A, Lewis lung carcinoma, metastatic model of the mammary carcinoma 1142A--a combined treatment consisting of vincristine--cyclophosphamide--metrotrexate--5-fluorouracil is superior to a combined treatment with carminomycin--dibromodulcitol. The treatment with carminomycin and dibromodulcitol in each case alone causes therapeutic benefits being superior to a treatment with the combination carminomycin--dibromodulcitol. This result could be stated for all tumor systems used. Carminomycin showed the greatest effectivity against the leukemia L1210. A human tumor nude mouse system--ascitic mesothelioma 1503A--is presented which is suitable for chemotherapeutic experiments. First test results indicated an antineoplastic effectivity after daunoblastin treatment, but cyclophosphamide and carminomycin did not influence the life span.

In plain English

This was a laboratory drug-testing study in mice. It did not study asbestos or asbestos exposure. The authors compared two cancer drug combinations, vincristine-cyclophosphamide-methotrexate-5-fluorouracil (VCMF) and carminomycin-dibromodulcitol (CD), and their single drugs. They used four mouse tumor systems with 10 animals per treatment group: leukemia L1210, mammary carcinoma 1142A (in muscle and as a metastasis model) and Lewis lung carcinoma. VCMF gave better results than CD in all four systems. The benefit of CD could also be reached with carminomycin alone in all systems, and with dibromodulcitol alone in all except leukemia L1210. The authors also tested a human mesothelioma line, 1503A, grown in nude mice from cells of a patient's peritoneal ascitic effusion. Untreated mice lived 9.6 plus or minus 1.8 days (females) and 10.8 plus or minus 1.9 days (males). Daunoblastin lengthened life span at some doses (31% at 6.8 mg/kg in female mice) but not at 13.6 mg/kg. Cyclophosphamide and carminomycin did not, even at toxic doses. The authors concluded the line is suitable for drug testing but called these first results needing further tests.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Animal experiment: chemotherapy testing in mouse tumor systems and in a human tumor line grown in nude mice
• Who was studied: Mice aged 4-6 weeks weighing 20-23 g, 10 per treatment group. The mice carried leukemia L1210, mammary carcinoma 1142A (intramuscular and metastasis models) or Lewis lung carcinoma. Separately, Balb/c nude mice carried the human mesothelioma line 1503A, derived from malignant cells of a peritoneal ascitic effusion. Work was done at the Central Institute of Cancer Research, Berlin-Buch (GDR).
• Exposure: No asbestos exposure was studied. The exposures were cancer drugs: the combinations VCMF and CD and their single components, given at three dose levels (LD10, LD10/2, LD10/4). In the mesothelioma line, carminomycin, daunoblastin and cyclophosphamide were tested.
• Main results:
  • Leukemia L1210: both combinations worked best at LD10/2, where VCMF gave a 186% increase in life span and CD gave 94% (Table VI).
  • Leukemia L1210: carminomycin alone at LD10 gave the largest increase in life span, 218% (Table VI). The authors took this to indicate the combination was unnecessary.
  • Intramuscular mammary carcinoma 1142A: LD10 doses of both combinations strongly inhibited tumor growth, but all animals were dead by day 14. VCMF was again superior to CD.
  • Lewis lung carcinoma: VCMF was superior to CD, and the single components of CD did favorably when given alone.
  • Metastasis model of 1142A: the best balance of metastasis inhibition and acceptable toxicity came from three treatments of VCMF at LD10/4.
  • Human mesothelioma line 1503A: after cells from the cultured peritoneal ascitic effusion were injected into the abdomen, mesothelioma findings developed in nude mice. Untreated mice given 1 million cells survived 9.6 plus or minus 1.8 days (females) and 10.8 plus or minus 1.9 days (males).
  • Mesothelioma 1503A: daunoblastin showed an antineoplastic effect at some doses. Increases in life span were 31% at 1 x 6.8 mg/kg and 30% at 3 x 6.8 mg/kg in females, and 42% at 1 x 6.8 mg/kg and 71% at 2 x 6.8 mg/kg in males.
  • Mesothelioma 1503A: at higher single doses of daunoblastin there was no increase in life span. At 1 x 13.6 mg/kg the increase was 0% in females, with 2 of 5 dying without tumor findings, and 0% in males, with 2 of 6. At 1 x 10.2 mg/kg in males it was 0%, with 1 of 5.
  • Mesothelioma 1503A: cyclophosphamide and carminomycin were not effective even though toxic doses were used, as shown by animals dying without tumor findings.
• The authors' conclusion: The authors concluded that CD could not be shown to be superior or even equal to VCMF, and that there was no compelling need to combine carminomycin and dibromodulcitol. They also concluded that the human mesothelioma line 1503A is suitable for chemotherapy experiments, but that its real value still had to be established by further tests.
• Limitations the authors state:
  • The mesothelioma 1503A results were first results; experiments with the other drugs of VCMF and CD were still in progress.
  • In the Lewis lung carcinoma results, some values came from groups in which only a few animals were still alive.

Topics

Medical terms in this study, explained in our Lexicon: Carcinoma, Fluorouracil (5-FU), Mesothelioma.

Related studies

• In vitro and in vivo therapeutic efficacy of the PPAR-γ agonist troglitazone in combination with cisplatin against malignant pleural mesothelioma cell growth — N. Hamaguchi, H. Hamada, et al. (2010)
• Network analysis of immunotherapy-induced regressing tumours identifies novel synergistic drug combinations — W.J. Lesterhuis, C. Rinaldi, et al. (2015)
• In vitro screening of synergistic ascorbate-drug combinations for the treatment of malignant mesothelioma — S. Martinotti, E. Ranzato, et al. (2011)
• Interferon-alpha and -gamma in combination with chemotherapeutic drugs: in vitro sensitivity studies in four human mesothelioma cell lines — A.M. Hand, K. Husgafvel-Pursiainen, et al. (1992)
• Experimental assessment of photodynamic therapy with chlorins for malignant mesothelioma — H.B. Ris, A. Giger, et al. (1997)
• IL4I1: an inhibitor of the CD8⁺ antitumor T-cell response in vivo — F. Lasoudris, C. Cousin, et al. (2011)

Browse more research in Oncology, or return to medical research.