Summary
Intraperitoneal (I.P.) administration of chemotherapeutic agents, in particular, cisplatin and bleomycin is successfully used in the treatment of ovarian1–5 and gastrointestinal malignancies6–7. Their use however, is limited by the rapid development of adhesions8–9. The vinca alkaloid group of chemotherapeutic agents has been shown to impair the acute inflammatory reaction10, which plays an important role in adhesion formation, thereby providing the rationale for addition of vindesine to an I.P. regimen containing cisplatin and bleomycin. A rat model was used to study the effects of various I.P. chemotherapeutic regimens on adhesion formation. Four groups were studied (30 rats/ Group). Regimens used included Group A (Saline), Group B (Vindesine 0.1 mg/ kg), Group C (Cisplatin 5 mg/kg and Bleomycin 0.2 mg/kg), and Group D (Cisplatin 5 mg/kg, Bleomycin 0.2 mg/ kg and Vindesine 0.1 mg/kg). In order to grade adhesion formation, animals were sacrificed on days 2, 14 and 28, with the severity of adhesions graded on a scale of I–IV in order of increasing severity. Adhesion formation in Group A (Saline) and Group B (Vindesine) was similar. The addition of Vindesine to Group C (Cisplatin and Bleomycin) resulted in a significant reduction in adhesion formation (p<0.01). The results of this experimental study suggest that the local toxicity of I.P. chemotherapy may be reduced by the inclusion of a vinca alkaloid
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Markman, M. Intraperitoneal chemotherapy for malignant diseases of the gastrointestinal tract Surg. Gynae. Obs. 1987: 164, 89–93
Howell, S. B., Pfeifle, C. E., Wung, W. C. et al. Intraperitoneal cisplatin with systemic thiosulphate protection. Ann. Intern. Med. 1982: 97, 845–851.
Markman, M., Howell, S. B., Pfeifle, C. E. et al. Intraperitoneal chemotherapy with high dose cisplatin and cytarabine in patients with refractory ovarian carcinoma and other malignancies confined to the abdominal cavity. Proc. Am. Soc. Clin. Oncol. 1984: 3, 165.
Markman, M., Green, M.R., Pfeifle, C. E. et al. Combination interactivity chemotherapy in patients with stage III-IV ovarian carcinoma failing standard regimens (abstr). Proc. Am. Soc. Clin. Oncol. 1983: 2, 147.
Lucas, W. E., Markman, M., Howell, S. B. Intraperitoneal chemotherapy for advanced ovarian carcinoma. Am. J. Obs. Gynae. 1985: 152, 474–478.
Cuncliffe, W. J., Sugarbaker, P. H. Gastrointestinal malignancy: rationale for adjuvant therapy using early postoperative intraperitoneal chemotherapy. Br. J. Surg. 1989: 76, 1082–1090.
Gianola, F. J., Sugarbaker, P. H., Barofsky, I. et al. Toxicity studies of adjuvent intravenous versus intraperitoneal 5-FU in patients with advanced primary colon or rectal cancer. Am. J. Clin. Oncol. 1986: 9, 403–10.
Markman, M., Cleary, S., Howell, S. B., Lucas, W. E. Complications of extensive adhesion formation after intraperitoneal chemotherapy. Surg. Gynae. Obs. 1986: 162, 445–448.
Litterest, C. L., Collins, J. M., Lowe, M. C., Arnold, S. T. et al. Local and systemic toxicity from large-volume intraperitoneal administration of doxorubicin in the rat Cancer Treat. Rep. 1982: 66, 157–161.
Cohen, S. C., Gabelnick, H. L., Johnson, R. K., Goldin, A. Effects of antineoplastic agents on wound healing in mice. Surg. 1975: 78, 238–244.
Markman, M., Cleary, S., Lucas, W., Weiss, R., Howell, S. B. Intraperitoneal chemotherapy employing a regimen of cisplatin, cytarabine, and bleomycin. Cancer Treat. Rep. 1986: 70, 755–760.
Young, R. C., Chabner, B. A., Hubbard, S. P. et al. Advanced ovarian adenocarcinoma: a prospective clinical trial of melphalan (L-PAM) versus combination chemotherapy. N. Eng. J. Med. 1978: 299, 1261–1266.
Israel, A. et al. Treatment of advanced epithelial ovarian cancer with a Ci-dichloro-diamine platinum, cyclophosphamide, and bleomycin combination. Am. J. Clin. Oncol. 1988: 11, 7–11.
Unpublished data.
Dendrick, R. L., Meyers, C. E., Bungay, P. M., De Vita, V. T. Pharmokinetic rationale for peritoneal drug administration in the treatment of ovarian carcinoma. Cancer Treat. Rep. 1978: 62, 1–11.
Jones, R. B., Myers, C. E., Guarino, A. M. et al. High volume intraperitoneal chemotherapy (belly bath) for ovarian cancer. Cancer, Chemother. Pharmacol. 1978: 1, 161–166.
Kaplan, R. A., Markman, M., Lucas, W. E., Pfeifle, C., Howell, S. B. Infectious peritonitis in patients receiving intraperitoneal chemotherapy. Amer. J. Med. 1985: 78, 49–53.
Ozols, R. F., Young, R. C., Speyer, J. L. et al. Phase 1 and pharmacologic studies of adriamycin administered intraperitoneally to patients with ovarian carcinoma. Cancer Research 1982: 42, 4265–9.
Bradley, J. A., McWhinnie, D. L., Hamilton, M. D. et al. Sclerosing obstructive peritonitis after continuous ambulatory peritoneal dialysis. Lancet 1983: 2, 113–114.
Levinson, C. J., Swolin, K. Postoperative adhesions: etiology, prevention, and therapy. Clin. Obstet Gynae. 1980: 23, 1213–1220.
Raftery, A.T. Effect of peritoneal trauma on peritoneal fibrinloytic activity and intraperitoneal adhesion formation. Eur. Surg. Res. 1981: 13, 397–401.
Buckman, R. F., Woods, M., Sargent, L., Gervin, A. A unifying pathogenic mechanism in the etiology of intraperitoneal adhesions. J. Surg. Research 1976: 20, 1–5.
Thompson, J. N., Paterson-Brown, S., Harboume, T., Whawell, S. A., Kalodiki, E., Dudley, H. A. F. Reduced human peritoneal plasminogen activating activity: possible mechanism of adhesion formation. Br. J. Surg. 1989: 76, 382–384.
Gunderson, S. Dacarbazine, Vindesine and Cisplatin combination chemotherapy in advanced malignant melanoma; a phase II study. Cancer Treat. Rep. 1987: 71, 997–9.
Postmus, P. E. et al. Cisplatin and Vindesine, a phase II study in lung cancer. J. Cancer Res. Clin. Oncol. 1987: 113, 99–100.
Kuhbock, J. et al. Palliative and adjuvant chemotherapy of metastatic renal cancer. Semin Surg. Oncol. 1988: 4, 116–23.
Rhomberg, W. U. Vindesine for recurrent and metastatic cancer of the uterine cervix: a phase II trial. Cancer Treat. Rep. 1986: 70, 1455–1457.
Willemse, P. H. et al. Long tern suurvival after vinblastine, bleomycin and cisplatin treatment in patients with germ cell tumours of the ovary; an update. Gynaecol. Oncol. 1987: 28, 268–277.
Hill, B. T., Whelan, D. H. Comparative effects of vincristine and vindesine on cell cycle kinetics in vitro. Cancer Treat. Rev. 1980: 7 (Supplement), 5–15.
Argenta, L. C., Manders, E. K. Mitomycin C extravasation injuries. Cancer 1983: 51, 1082–2.
Surwit, E. A. etal. Phase II trial of Vinblastine in previously treated patients with ovarian cancer, a Southwest Oncology Group Study. Gynaecol. Oncol. 1987: 28, 14–19.
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Molloy, R.G., Crowley, B., Moran, K.T. et al. Reduction of the local toxicity of intraperitoneal chemotherapy; an experimental model. I.J.M.S. 159, 175–177 (1990). https://doi.org/10.1007/BF02937237
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DOI: https://doi.org/10.1007/BF02937237