Cisplatin combined with the new cisplatin-procaine complex DPR

In vitro and in vivo studies

M. Viale, M. O. Vannozzi, F. Merlo, S. Cafaggi, B. Parodi, M. Esposito

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

The administration of combinations of platinum compounds is considered as a useful alternative therapeutic strategy to avoid the complications of toxic events during cancer chemotherapy in order to obtain a therapeutic advantage. On the basis of previous in vitro and in vivo findings, suggesting an antitumour activity of the new cisplatin-derived compound cis-diamminechloro-[2-(diethylamino)ethyl 4-amino-benzoate, N4]-chlorideplatinum(II) monohydrochloride monohydrate (DPR), we investigated the effectiveness of the combination of cisplatin (DDP) and DPR in vitro on murine leukaemic cells, which were either sensitive (P388) or resistant (L1210/DDP) to DDP, and on the murine M5076 reticulum cell sarcoma, and in vivo in BDF1 female mice transplanted with P388 leukaemic cells or cisplatin-resistant L1210/DDP leukaemic cells. The contemporaneous exposure in vitro to both platinum compounds gave a significantly higher cell growth inhibition than that expected on the basis of dose-response curves for single agents in all tumour models tested. In vivo, the combinations of DDP plus DPR elicited significant enhancement over the activity of the drugs alone both in the ascitic and solid P388 models. The combined treatment of 10 mg/kg DDP and 14 mg/kg DPR yielded 62.5% tumour-free mice compared with 6.2% with 10 mg/kg DDP alone, the best single agent. It is noteworthy that the combined application of DDP and DPR was also very effective in the solid cisplatin-resistant L1210/DDP model, inducing a significant reduction in the volume of tumour. A therapeutic advantage was achieved with combination treatments that had no effect on platinum-mediated body weight loss and were generally well tolerated by the mice. At equitoxic concentrations of DPR and carboplatin, the treatment with DDP plus DPR proved to have a higher efficacy against this tumour model compared to that observed after the combined treatment with DDP and carboplatin. In summary, the combination of DDP and DPR showed a therapeutic advantage over single drug treatment and has demonstrated promise at the preclinical level in its ability to circumvent acquired resistance to DDP both in vitro and in vivo.

Original languageEnglish
Pages (from-to)2327-2333
Number of pages7
JournalEuropean Journal of Cancer
Volume32
Issue number13
DOIs
Publication statusPublished - Dec 1996

Fingerprint

Cisplatin
Platinum Compounds
Carboplatin
Neoplasms
Therapeutics
Poisons
Benzoates
Platinum
Tumor Burden
Pharmaceutical Preparations
Non-Hodgkin's Lymphoma
In Vitro Techniques
cisplatin-procaine complex
Weight Loss
Body Weight
Drug Therapy
Growth

Keywords

  • Cisplatin
  • Cisplatin-procaine complex
  • Combined action in vitro and in vivo

ASJC Scopus subject areas

  • Cancer Research
  • Hematology
  • Oncology

Cite this

Cisplatin combined with the new cisplatin-procaine complex DPR : In vitro and in vivo studies. / Viale, M.; Vannozzi, M. O.; Merlo, F.; Cafaggi, S.; Parodi, B.; Esposito, M.

In: European Journal of Cancer, Vol. 32, No. 13, 12.1996, p. 2327-2333.

Research output: Contribution to journalArticle

Viale, M. ; Vannozzi, M. O. ; Merlo, F. ; Cafaggi, S. ; Parodi, B. ; Esposito, M. / Cisplatin combined with the new cisplatin-procaine complex DPR : In vitro and in vivo studies. In: European Journal of Cancer. 1996 ; Vol. 32, No. 13. pp. 2327-2333.
@article{cf9e9d4717ed46dcb719fc88daf0d6d6,
title = "Cisplatin combined with the new cisplatin-procaine complex DPR: In vitro and in vivo studies",
abstract = "The administration of combinations of platinum compounds is considered as a useful alternative therapeutic strategy to avoid the complications of toxic events during cancer chemotherapy in order to obtain a therapeutic advantage. On the basis of previous in vitro and in vivo findings, suggesting an antitumour activity of the new cisplatin-derived compound cis-diamminechloro-[2-(diethylamino)ethyl 4-amino-benzoate, N4]-chlorideplatinum(II) monohydrochloride monohydrate (DPR), we investigated the effectiveness of the combination of cisplatin (DDP) and DPR in vitro on murine leukaemic cells, which were either sensitive (P388) or resistant (L1210/DDP) to DDP, and on the murine M5076 reticulum cell sarcoma, and in vivo in BDF1 female mice transplanted with P388 leukaemic cells or cisplatin-resistant L1210/DDP leukaemic cells. The contemporaneous exposure in vitro to both platinum compounds gave a significantly higher cell growth inhibition than that expected on the basis of dose-response curves for single agents in all tumour models tested. In vivo, the combinations of DDP plus DPR elicited significant enhancement over the activity of the drugs alone both in the ascitic and solid P388 models. The combined treatment of 10 mg/kg DDP and 14 mg/kg DPR yielded 62.5{\%} tumour-free mice compared with 6.2{\%} with 10 mg/kg DDP alone, the best single agent. It is noteworthy that the combined application of DDP and DPR was also very effective in the solid cisplatin-resistant L1210/DDP model, inducing a significant reduction in the volume of tumour. A therapeutic advantage was achieved with combination treatments that had no effect on platinum-mediated body weight loss and were generally well tolerated by the mice. At equitoxic concentrations of DPR and carboplatin, the treatment with DDP plus DPR proved to have a higher efficacy against this tumour model compared to that observed after the combined treatment with DDP and carboplatin. In summary, the combination of DDP and DPR showed a therapeutic advantage over single drug treatment and has demonstrated promise at the preclinical level in its ability to circumvent acquired resistance to DDP both in vitro and in vivo.",
keywords = "Cisplatin, Cisplatin-procaine complex, Combined action in vitro and in vivo",
author = "M. Viale and Vannozzi, {M. O.} and F. Merlo and S. Cafaggi and B. Parodi and M. Esposito",
year = "1996",
month = "12",
doi = "10.1016/S0959-8049(96)00354-1",
language = "English",
volume = "32",
pages = "2327--2333",
journal = "European Journal of Cancer",
issn = "0959-8049",
publisher = "Elsevier Ltd",
number = "13",

}

TY - JOUR

T1 - Cisplatin combined with the new cisplatin-procaine complex DPR

T2 - In vitro and in vivo studies

AU - Viale, M.

AU - Vannozzi, M. O.

AU - Merlo, F.

AU - Cafaggi, S.

AU - Parodi, B.

AU - Esposito, M.

PY - 1996/12

Y1 - 1996/12

N2 - The administration of combinations of platinum compounds is considered as a useful alternative therapeutic strategy to avoid the complications of toxic events during cancer chemotherapy in order to obtain a therapeutic advantage. On the basis of previous in vitro and in vivo findings, suggesting an antitumour activity of the new cisplatin-derived compound cis-diamminechloro-[2-(diethylamino)ethyl 4-amino-benzoate, N4]-chlorideplatinum(II) monohydrochloride monohydrate (DPR), we investigated the effectiveness of the combination of cisplatin (DDP) and DPR in vitro on murine leukaemic cells, which were either sensitive (P388) or resistant (L1210/DDP) to DDP, and on the murine M5076 reticulum cell sarcoma, and in vivo in BDF1 female mice transplanted with P388 leukaemic cells or cisplatin-resistant L1210/DDP leukaemic cells. The contemporaneous exposure in vitro to both platinum compounds gave a significantly higher cell growth inhibition than that expected on the basis of dose-response curves for single agents in all tumour models tested. In vivo, the combinations of DDP plus DPR elicited significant enhancement over the activity of the drugs alone both in the ascitic and solid P388 models. The combined treatment of 10 mg/kg DDP and 14 mg/kg DPR yielded 62.5% tumour-free mice compared with 6.2% with 10 mg/kg DDP alone, the best single agent. It is noteworthy that the combined application of DDP and DPR was also very effective in the solid cisplatin-resistant L1210/DDP model, inducing a significant reduction in the volume of tumour. A therapeutic advantage was achieved with combination treatments that had no effect on platinum-mediated body weight loss and were generally well tolerated by the mice. At equitoxic concentrations of DPR and carboplatin, the treatment with DDP plus DPR proved to have a higher efficacy against this tumour model compared to that observed after the combined treatment with DDP and carboplatin. In summary, the combination of DDP and DPR showed a therapeutic advantage over single drug treatment and has demonstrated promise at the preclinical level in its ability to circumvent acquired resistance to DDP both in vitro and in vivo.

AB - The administration of combinations of platinum compounds is considered as a useful alternative therapeutic strategy to avoid the complications of toxic events during cancer chemotherapy in order to obtain a therapeutic advantage. On the basis of previous in vitro and in vivo findings, suggesting an antitumour activity of the new cisplatin-derived compound cis-diamminechloro-[2-(diethylamino)ethyl 4-amino-benzoate, N4]-chlorideplatinum(II) monohydrochloride monohydrate (DPR), we investigated the effectiveness of the combination of cisplatin (DDP) and DPR in vitro on murine leukaemic cells, which were either sensitive (P388) or resistant (L1210/DDP) to DDP, and on the murine M5076 reticulum cell sarcoma, and in vivo in BDF1 female mice transplanted with P388 leukaemic cells or cisplatin-resistant L1210/DDP leukaemic cells. The contemporaneous exposure in vitro to both platinum compounds gave a significantly higher cell growth inhibition than that expected on the basis of dose-response curves for single agents in all tumour models tested. In vivo, the combinations of DDP plus DPR elicited significant enhancement over the activity of the drugs alone both in the ascitic and solid P388 models. The combined treatment of 10 mg/kg DDP and 14 mg/kg DPR yielded 62.5% tumour-free mice compared with 6.2% with 10 mg/kg DDP alone, the best single agent. It is noteworthy that the combined application of DDP and DPR was also very effective in the solid cisplatin-resistant L1210/DDP model, inducing a significant reduction in the volume of tumour. A therapeutic advantage was achieved with combination treatments that had no effect on platinum-mediated body weight loss and were generally well tolerated by the mice. At equitoxic concentrations of DPR and carboplatin, the treatment with DDP plus DPR proved to have a higher efficacy against this tumour model compared to that observed after the combined treatment with DDP and carboplatin. In summary, the combination of DDP and DPR showed a therapeutic advantage over single drug treatment and has demonstrated promise at the preclinical level in its ability to circumvent acquired resistance to DDP both in vitro and in vivo.

KW - Cisplatin

KW - Cisplatin-procaine complex

KW - Combined action in vitro and in vivo

UR - http://www.scopus.com/inward/record.url?scp=0030446475&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030446475&partnerID=8YFLogxK

U2 - 10.1016/S0959-8049(96)00354-1

DO - 10.1016/S0959-8049(96)00354-1

M3 - Article

VL - 32

SP - 2327

EP - 2333

JO - European Journal of Cancer

JF - European Journal of Cancer

SN - 0959-8049

IS - 13

ER -