Abstract
Although 50%–80% of patients with advanced ovarian cancer demonstrate an objective response after platinum-based chemotherapy, a majority of these patients will ultimately experience a relapse of their disease. Effective second-line treatment for these patients is of the utmost importance. We performed a phase II study with cisplatin and pirarubicin (each drug 50 mg/m2 i.v. every 28 days) in 17 patients with relapsed or persistent ovarian carcinoma. All patients had received platinum-containing primary chemotherapy. Overall survival from the time of diagnosis was 38.3 months (45.3 months in relapsed ovarian carcinoma and 28.3 months in ovarian carcinoma persisting after primary chemotherapy). Survival from entrance into the study was 13.0 months (14.2 months in relapsed disease and 11.2 months in refractory disease). Time to progression was 10.3 months. An objective response was observed in 4 patients and another 3 patients had stable disease. Major toxicity consisted of emesis (grade III/IV in 60/64 courses) and myelosuppression WHO grade III/IV in 15 courses. Neurotoxicity occurred in 3 patients and nephrotoxicity in 1 patient. Alopecia occurred in 12 patients. Tachycardia and other low-grade heart toxicities were observed after 5 courses. Dose reduction was necessary because of severe myelosuppression in 4 courses and because of nephrotoxicity in 1 course. Delay of subsequent chemotherapy courses for more than 7 days was necessary after 13 courses and was always due to myelosuppression. The dose-limiting toxicity of combination chemotherapy with cisplatin and pirarubicin is myelosuppression. Response and survival rates are superior in patients with relapsed disease compared to patients with resistent ovarian carcinoma.
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References
Advanced Ovarian Cancer Trialist Group (1991) Chemotherapy in advanced ovarian cancer: an overview of randomized trials. Br Med J 303:884–893
Barker GH, Wiltshaw E (1981) Use of high dosecis-dichlorodiammine platinum (II) following failure on previous chemotherapy for advanced carcinoma of the ovary. Br J Obstet Gynecol 88:1192–1199
Benjamin RS, Fenoglio C, Hortobagyi GN et al. (1990) Cardiotoxicity of pirarubicin. Proc Annu Meet Am Assoc Cancer Res 31:A1060
Berthaud P, Le Chevalier T, Berille J et al. (1989) Phase II study of pirarubicin in advanced non-small cell lung cancer. Eur J Cancer 25:1507–1508
Bois A du, Meerpohl HG, Vach W, Kommoss FGM, Fenzl E, Pfleiderer A (1992) Course, patterns, and risk-factors for chemotherapy-induced emesis in cisplatin-pretreated patients: a study with ondansetron. Eur J Cancer 28:450–457
Bremer K, Rieche K, Essers U, Queißer U (1989) Pirarubicin in advanced low-grade malignant non-Hodgkin's lymphomas. Contrib Oncol 37:119–124
Bronchud MH, Howell A, Crowther D, Hopwood P, Souza I, Dexter TM (1989) The use of granulocyte conoly-stimulating factor to increase the intensity of treatment with doxorubicin in patients with advanced breast and ovarian cancer. Br J Cancer 60:121–125
Bruckner HW, Wallach R, Cohen CJ et al. (1981) High dose platinum for the treatment of refractory ovarian cancer. Gynecol Oncol 12:64–67
Coleman R, Towlson E, Wiltshaw E et al (1990) Epirubicin for pretreated advanced ovarian cancer. Eur J Cancer 26:850–851
Drings P, Tessen HW, Gatzemeier U et al. (1989) Phase II study of pirarubicin (THP-doxorubicin) in advanced non-small cell lung cancer. Contrib Oncol 37:103–113
Eckhardt S, Hermadi Z, Thurzo L et al. (1990) Phase II clinical evaluation od etoposide as a second-line treatment in ovarian cancer. Oncology 47:289–295
Gore ME, Fryatt I, Wiltshaw E, Dawson T (1990) Treatment of relapsed carcinoma of the ovary with cisplatin or carboplatin following initial treatment with these compounds. Gynecol Oncol 36:207–211
Hainsworth JD, Grosh WW, Burrett LS et al. (1988) Advanced ovarian cancer: long term results of treatment with intensive cisplatin-based chemotherapy of brief duration. Ann Intern Med 108:165–170
Harstrick A, Casper J, Koehne-Woemper H, Wilke H, Schmoll HJ, Poliwoda H (1990) Comparative activity of four anthracyclines against heterotransplanted germ cell tumor lines. Invest New Drugs 8:19–24
Henss A, Arnold H, Fiebig HH, Loehr GW (1989) Phase II study of pirarubicin in small cell lung carcinoma. Contrib Oncol 37:114–118
Herait P, Poutignat N, Marty M, Bugat R (1992) Early assessment of a new anticancer drug analogue-are the historical comparisons obsolete? The French experience with pirarubicin. Eur J Cancer 28A:1670–1676
Inoue K, Arakowa M, Miyamoto H, Ogawa M (1983) Activity of 4′-O-tetrahydropyranyl-Adriamycin hydrochloride (THP-Adriamycin) in a human tumor cloning system. Invest New Drugs 1:271–275
Iro H, Koenig HJ (1990) Phase II Studie mit Pirarubicin bei vorbehandeltem progredienten Kopf-Hals-Malignomen. Laryngorhinootologie 69:131–134
Kleeberg UR, Reichel L, Wander HE et al. (1990) Phase II study of pirarubicin in metastatic breast cancer. Onkologie 13:175–179
Levi F, Benavides M, Chevelle C et al. (1990) Chemotherapy of advanced ovarian cancer with 4′-O-tetrahydropyranyl doxorubicin and cisplatin: a randomized phase II trial with an evaluation of circadian timing and dose-intensisty. J Clin Oncol 8:705–714
Louie KG, Ozols RF, Myers LE et al. (1986) Long term results of a cisplatin-containing combination chemotherapy regimen for the treatment of advanced ovarian carcinoma. J Clin Oncol 4:1579–1585
Markman M, Hoskins W (1992) Response to salvage chemotherapy in ovarian cancer: a critical need for precise definitions of the treated population (Editorial). J Clin Oncol 10:513–514
Markman M, Rothman R, Hakes T et al. (1991) Second-line platinum therapy in patients with ovarian cancer previously treated with cisplatin. J Clin Oncol 9:389–393
McGuire WP, Rowinsky EK, Rosensheim NB et al. (1989) Taxol: a unique antineoplastic agent with significant activity in advanced ovarian epithelial neoplasm. Ann Intern Med 111:273–279
Menczer J, Baitner S, Modan M, Chaitchik S, Brenner H (1981) Response to second line chemotherapy in ovarian cancer of epithelial origin. Eur J Cancer Clin Oncol 17:1259–1262
Mickisch GH, Gottesman MM, Pastan L (1992) New chemosensitizers to reverse multidrug resistance in renal cell carcinoma and in mdrtransgenic mice (abstract 597). Proc ASCO 11:196
Miller AA, Schmidt CG (1987) Clinical pharmacology and toxicity of 4′-O-tetrahydropyranyladriamycin. Cancer Res 47:1461–1465
Miller AB, Hogstraten B, Staquet M (1981) Reporting results of cancer treatment. Cancer 47:207–214
Neijt JP (1992) Treatment of advanced ovarian cancer: 10 years of experience. Ann Oncol 3:17–27
Ovarian Cancer Meta-analysis Project (1991) Cyclophosphamide plus cisplatin versus cyclophosphamide, doxorubicin, and cisplatin chemotherapy of ovarian carcinoma: a meta-analysis. J Clin Oncol 9:1668–1674
Ozols RF, Ostchega Y, Curt G, Young RC (1987) High-dose carboplatin in refractory ovarian cancer patients. J Clin Oncol 5:197–201
Redman C, Lawton F, Stuart N et al. (1989) Phase II study of combination 4′-epidoxorubicin and mitomycin C in recurrent epithelial ovarian cancer. Cancer Chemother Pharmacol 23:51–53
Saito T, Kasai Y, Wakin A et al. (1986) Phase II study of (2″R-(4′-O-tetrahydropyranyl-Adriamycin (THP) in patients with solid tumors. Jpn J Cancer Chemother 13:1060–1069
Scheithauer W, Samonigg H, Depisch D et al. (1990) Pirarubicin for treatment of advanced breast cancer. Invest New Drugs 8:207–210
Schroeder M, Donhuijsen-Ant R, Purea H, Westerhausen M (1989) Clinical experience with pirarubicin in the treatment of patients with pretreated head and neck cancer. Contrib Oncol 37:74–77
Spielmann M, Kerbat P, Delozier T et al. (1990) Pirarubicin in advanced breast cancer: French cooperative phase II study. Eur J Cancer 26:821–823
Sridhar KS, Hussein AM, Feun LG, Zubrod CG (1989) Activity of pirarubicin in malignant mesothelioma. Cancer 63:1084–1091
Sridhar KS, Samy SA, Agarwal RP et al. (1990) A phase II study of 4′-O-tetrahydropyranyladriamycin. Cancer 66:2082–2091
Thigpen T, Blessing J, Ball H et al. (1990) Phase II trial of taxol as second-line therapy for ovarian carcinoma: Gynecologic Oncology Group study. Proc Am Assoc Clin Oncol 9:A156
Tominaga T, Abe O, Enomoto K et al. (1989) A randomized controlled study of (2″R)-4′-O-tetrahydropyranyladriamycin and Adriamycin in combination with cyclophosphamide and 5-fluorouracil in the treatment of advanced and recurrent breast cancer. Biomed Pharmacother 43:271–278
Untch M, Sevin BU, Perras J et al. (1992) Evaluation of chemosensitivity to pirarubicin and other chemotherapeutic agents in primary and recurrent gynecologic malignancies. Gynecol Oncol (in press)
Van der Burg MEL, Hoff AM, Lent M van, Rodenburg CJ, Putten WLJ van, Stoter G (1991) Carboplatin and cyclophosphamide salvage therapy for ovarian cancer patients relapsing after cisplatin combination chemotherapy. Eur J Cancer 27:248–250
Vermorken JB, Bokkel Huinnik WW ten, Kobierska A et al. (1990) Antitumor activity of high dose epirubicin in patients with ovarian cancer failing platinum-based regimens. Proc Am Assoc Cancer Res Annu Meet 31:A1117
Vermorken JB, Kobierska A, Zanaboni F et al. (1992) Phase II study of high-dose epirubicin in ovarian cancer patients previously treated with cisplatin. Ann Oncol 3 [Suppl 1]:A328
WHO (1979) Handbook for reporting the results of cancer treatment. WHO Offset Publ 48
Worst P, Fiebig HH, Harstrick A, Donhuijsen-Ant R, Edler L, Queißer W (1989) Pirarubicin in advanced soft tissue sarcomas. Contrib Oncol 37:78–88
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du Bois, A., Meerpohl, H.G., Madjar, H. et al. Phase II study of pirarubicin combined with cisplatin in recurrent ovarian cancer. J Cancer Res Clin Oncol 120, 173–178 (1994). https://doi.org/10.1007/BF01202198
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DOI: https://doi.org/10.1007/BF01202198