Summary
Phase II studies of p.o. Idarubicin administration, a new daunorubicin analogue (4-demethoxydaunorubicin), have shown antitumor activity in 23%–31% of previously treated metastatic breast cancer patients, while in untreated patients a response rate of 41% was observed. Our Phase II study has shown an overall response of 23% [1 complete response (CR), 9 partial response (PR), 10/43] with a daily dose of 15 mg/m2 p.o. on days 1, 2, 3. On the basis of these results we have recently included Idarubicin in combination chemotherapy of breast cancer, substituting Adriamycin by Idarubicin in an FAC schedule. Of 50 consecutive metastatic breast cancer patients who entered the study, 42 patients who received >2 cycles were evaluable. There were 22 premenopausal and 20 postmenopausal patients (mean=51 years). In 25 patients a performance status of 0–2 (ECOG) was registered and in 17 patients it was 3. Previous radiation had been administered in 34, hormonal therapy in 18, and adjuvant chemotherapy (CMF 5, CMFVP 3) in 8 patients; 22 patients had predominant metastatic sites in soft tissues, 18 in visceral organs, and 2 in the bones. The FIC schedule was administered as follows: 5-fluorouracil 500 mg/m2 i.v. days 1 and 8, Idarubicin 15 mg/m2 p.o. days 1,2 and 3, and cyclophosphamide 500 mg/m2 i.v. day 1. An objective response was observed in 23 (5 CR, 18 PR) out of 42 patients (53%, CR 12%). Soft tissue metastases responded in 55% (12/22), visceral organs in 61% (11/18), and no response was observed in bone lesions (0/2). The median remission duration was 8 months (3–16+). Toxicity was mild, expressed mainly in the form of nausea/vomiting, grade I and II in 64% of the patients. Alopecia was very mild (grade I and II in 23% of the patients). Leukopenia grade I–II was observed in 21% of the patients. In 4 patients reversible ECG changes occurred. Left ventricular ejection fraction did not show any pathological changes. The Idarubicin-containing combination chemotherapy we have used has the following characteristics: easier administration (p.o. anthracycline, no risk of tissue extravasation), lower toxicity (cardiotoxicity, alopecia, and myelosuppression in particular), and a notable antitumor activity.
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References
Arcamone F, Di Marco A, Casazza AM (1978) Chemistry and pharmacology of new antitumor anthracyclines. In: Advances in cancer chemotherapy. University Park Press, Baltimore, pp 279–312
Armand JP (1986) Epirubicin in the treatment of advanced breast cancer-an overview of clinical data. Symposium on Epirubicin, Abstracts 14th Int Cancer Congress, Budapest
Bastholt L, Ejlertsen B, Dalmark M (1986) Phase II study of 4-demethoxydaunorubicin by oral route in the treatment of anthracycline naive advanced breast cancer patients. XIV Int. Cancer Congress, Round table conference on Idarubicin, Abstracts, Budapest
Bonadonna G (1985) Comparative activity and toxicity of Doxorubicin (DX) a new anthracycline analog in advanced breast cancer. 14th Int Cancer Congress, Abstracts, Kyoto
Bonfante V, Ferrari L, Brambilla C, Rossi A, Villani F, Crippa F, Valagussa P, Bonadonna G (1986) New anthracycline analogs in advanced breast cancer. Eur J Cancer Clin Oncol 11:1379–1985
Casazza AM (1980) Experimental evaluation of anthracycline analogues. Cancer Treat Rep 63:833–844
Di Marco A, Casazza AM, Pratesi G (1979) Antitumor activity of 4-dimethoxydaunorubicin administered orally. Cancer Treat Rep 893-894
Formelli F, Casazza AM, Di Marco A, Mariani A, Pollini C (1979) 4-Demethoxydaunorubicin and 4-demethoxydoxorubicin in mice bearing solid tumors. Cancer Chem Pharmacol 3:261–269
Intini C (1986) Report of the Italian cooperative group on FAC vs. FEC chemotherapy in metastatic breast cancer. Round table conference: Antitumor activity of new anthracycline analogues, Abstracts, Zagreb
Kaplan S, Martini A, Varine M, Togni P, Cavelli F (1982) Phase I trial of 4-demethoxydaunorubicin with single i. v. dose. Br J Cancer Clin Oncol 19:1303–1306
Kolarié K, Vukas D, Potrebica V, Červek J, Cerar O (1985) Cyclophosphamide adriamycine and platinum (CAP) a new effective approach in the treatment of disseminated breast cancer. Tumori 71:159–165
Kolarié K, Vukas D, Potrebica V (1987) CAP vs. FAC combination chemotherapy in disseminated breast cancer. V Int Conference on Platinum compounds, Abstracts, Padova
Kolarié K, Potrebica V, Mechl Z, Sopkova B (1987) Phase II study of peroral 4-demethoxydaunorubicin in previously treated (antracycline naive) breast cancer patients. Oncology 44:82–86
Lauro L, Vici P, Papaldo P, Ganzina F, Lopez M (1986) Idarubicina e Ciclofosfamide per via orale nel Trattamanto del carcinoma mammario metastatizzato. IV Ruini one Nazionale di Oncologia Sperimentale e Clinica, Abstracts, Bari
Lionetto R, Pronzato P, Conte P, Sertoli M, Amoroso D, Rosso R (1986) Idarubicin in advanced breast cancer: a phase II study. Cancer Treat Rep 70:1439–1440
Lopez M, Di Lauro L, Papaldo P, Lazzaro B, Ganzina F, Di Pietro N (1986) Phase II trial with oral idarubicin in advanced breast cancer. Inv New Drugs 4:39–42
Martoni A, Pacciarini MA, Panutti F (1985) Activity of 4-demethoxydaunorubicin by the oral route in advanced breast cancer. Eur J Cancer Clin Oncol 21:803–806
Tranum BL, McDonald B, Thigpen T, Vaugh C, Costanzi J, Gad el Mawli N, Palmer R, Hoogstraten B, Heilburn M, Rasmusen S (1982) Adriamycin combinations in advanced breast cancer-A South West Oncology Study Group. Cancer 49:835–839
Wander HE, Mexer D, Schuff-Werner P, Nagel GA (1986) Phase II trial of oral Idarubicin in advanced breast cancer. Onkologie 9:236–238
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Kolarié, K., Potrebica, V., Vukas, D. et al. Combination chemotherapy with 5-Fluorouracil, oral Idarubicin, and cyclophosphamide (FIC) in metastatic breast cancer—an open Phase II study. J Cancer Res Clin Oncol 114, 301–305 (1988). https://doi.org/10.1007/BF00405838
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DOI: https://doi.org/10.1007/BF00405838