A comparison of two doses of adriamycin in the primary chemotherapy of disseminated breast carcinoma

123

Summary Two hundred and eleven patients with node-positive stage 11 and IlIl breast cancer were treated with eight cycles of adjuvant chemotherapy comprising cyclophosphamide, doxorubicin and oral ftorafur (CAFt), with and without tamoxifen. All patients had undergone radical surgery, and 148 patients were treated with post-operative radiotherapy in two randomized studies. The impact of haematological toxicity of CAFt on distant disease-free (DDFS) and overall survival (OS) was recorded. Dose intensity of all given cycles (Dl), dose intensity of the two initial cycles (Dl2) and total dose (TD) were calculated separately for all chemotherapy drugs and were correlated with DDFS and OS. Patients with a lower leucocyte nadir during the chemotherapy had significantly better DDFS and OS (P = 0.01 and 0.04 respectively). Dose intensity of the two first cycles also correlated significantly with DDFS (P=0.05) in univariate but not in multivariate analysis, while the leucocyte nadir retained its prognostic value. These results indicate that the leucocyte nadir during the adjuvant chemotherapy is a biological marker of chemotherapy efficacy; this presents the possibility of establishing an optimal dose intensity for each patient. The initial dose intensity of adjuvant chemotherapy also seems to be important in assuring the optimal effect of adjuvant chemotherapy.

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confidence: 99%

Haematological toxicity: a marker of adjuvant chemotherapy efficacy in stage II and III breast cancer

Saarto

Blomqvist²,

Rissanen³

et al. 1997

123

“…When the total dose of two regimes are equivalent, the dose intensity may be of critical importance as exemplified by the lower efficacy of 35 mg m-2 doxorubicin (q 3 weeks x 16) when compared to 70 mg m2 doxorubicin (q 3 weeks x 8) (Carmo-Pereira et al, 1987). In a randomised study comparing the effect of scheduling on treatment outcome, there was no difference bet*een the equi-dose intensive regimes of doxorubicin 25 mg M2 (weekly x 12) versus 75 mg m-2 (3 weekly x 4 (Richards et al, 1992).…”

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confidence: 99%

“…The objective response rates to doxorubicin are largely dose related. Low dose regimes (<60 mg m2 per 3 weeks) achieve a low response rate (approximately 30%) and a particularly low rate of complete remission (Gundersen et al, 1986;Carmo-Pereira et al, 1987;Gundersen et al, 1990;Jonsson et al, 1991). The response to conventional dose doxorubicin (60-70 mg m2 per 3 weeks) and to combination regimes containing doxorubicin are of the order of 50-60% (Carmo-Pereira et al, 1987;Steiner et al, 1983 and many others).…”

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confidence: 99%

“…Low dose regimes (<60 mg m2 per 3 weeks) achieve a low response rate (approximately 30%) and a particularly low rate of complete remission (Gundersen et al, 1986;Carmo-Pereira et al, 1987;Gundersen et al, 1990;Jonsson et al, 1991). The response to conventional dose doxorubicin (60-70 mg m2 per 3 weeks) and to combination regimes containing doxorubicin are of the order of 50-60% (Carmo-Pereira et al, 1987;Steiner et al, 1983 and many others). At high doses () 100 mg m-2 per 3 weeks) response rates of over 80% have been reported in breast cancer patients (Jones et al, 1987(Jones et al, , 1990Bronchud et al, 1989).…”

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confidence: 99%

See 1 more Smart Citation

High dose, dose-intensive chemotherapy with doxorubicin and cyclophosphamide for the treatment of advanced breast cancer

Ferguson

Dodwell²,

Seymour³

et al. 1993

Summary Eighteen patients with advanced breast cancer were commenced on treatment with high dose doxorubicin (100mg m2) or doxorubicin (100 mg m-2) and cyclophosphamide (500 mg m-2) at 2 weekly intervals. Three cycles of treatment were planned. rG-CSF was given subcutaneously for 10 days, starting 24 h after each cycle of chemotherapy. Sixteen out of 18 patients responded (89%) of whom six (33%) achieved a complete remission. Twelve (67%) completed the three planned cycles, four (22%) received two cycles and two (11%) received one cycle only. The median time to progression was 51 months and the median survival was 18j months. Neutropenia occurred after 89% of courses and 65% of courses were accompanied by a significant (WHO grade III or IV) infection. The duration of neutropenia was short (mean 5.4 Gundersen et al., 1990;Jonsson et al., 1991). The response to conventional dose doxorubicin (60-70 mg m2 per 3 weeks) and to combination regimes containing doxorubicin are of the order of 50-60% (Carmo-Pereira et Steiner et al., 1983 and many others). At high doses () 100 mg m-2 per 3 weeks) response rates of over 80% have been reported in breast cancer patients (Jones et al., 1987(Jones et al., , 1990Bronchud et al., 1989). Cyclophosphamide shows a similar, if less dramatic increase in effectiveness at increasing doses (Bramwell et al., 1983;Frei et al., 1989).The importance of drug scheduling and dose intensity on efficacy and toxicity of treatment have been increasingly appreciated. When the total dose of two regimes are equivalent, the dose intensity may be of critical importance as exemplified by the lower efficacy of 35 mg m-2 doxorubicin (q 3 weeks x 16) when compared to 70 mg m2 doxorubicin (q 3 weeks x 8) (Carmo-Pereira et al., 1987). In a randomised study comparing the effect of scheduling on treatment outcome, there was no difference bet*een the equi-dose intensive regimes of doxorubicin 25 mg M2 (weekly x 12) versus 75 mg m-2 (3 weekly x 4 (Richards et al., 1992). The relative importance of these two parameters is unknown when high dose doxorubicin is used. In a previous study by Bronchud et al. (1989) The question then arises whether reducing the dose of doxorubicin further, whilst maintaining a dose intensive schedule would result in lesser toxicity without loss of treatment efficacy. To this end we have investigated the effects of doxorubicin given at 100 mg m2 at 2 weekly intervals in 18 patients with metastatic breast cancer. The first nine patients also received 500 mg m-2 cyclophosphamide and dose acceleration up to 2000 mg m-2 was intended. The epithelial toxicity of the combination chemotherapy appeared greater than expected and in consequence the remaining nine patients were treated with doxorubicin alone.The major toxicity of this regime was expected to be myelosuppression, particularly neutropenia. Myelosuppressive effects of chemotherapy can be mitigated in part by use of recombinant haemopoietic growth factors which stimulate the proliferation and maturation of haemopoietic cells in the b...

“…Treatment was (Steiner et al, 1983) and is more effective at high (70 mg m2) than low (35 mg m2) doses (Carmo-Pereira et al, 1987). However, because anthracyclines are metabolised by the liver, elimination is delayed in patients with liver dysfunction (Benjamin et al, 1984).…”

Section: Methodsmentioning

confidence: 99%

Weekly epirubicin for breast cancer with liver metastases and abnormal liver biochemistry

Twelves

O'Reilly²,

Coleman³

et al. 1989

Self Cite

Summary Thirty-six consecutive patients with breast cancer and liver metastases with abnormal liver biochemistry were treated with epirubicin 25 mg m-2 i.v. weekly. No dose modification was made for abnormal liver biochemistry, but dose intensity was adjusted by delaying treatment according to myelosuppression. The UICC overall response rate according to UICC criteria was 11/36 (30%) and median response duration was 27 weeks. Liver biochemistry improved in a further seven patients. Treatment was well tolerated. Epirubicin given in this way is effective in patients with breast cancer and liver metastases. An initial deterioration in liver biochemistry may occur before there is a response to epirubicin.Liver metastases are common in patients with advanced breast cancer. The prognosis is worse for these patients than after recurrence in either soft tissue (Fentiman et al., 1986) or bone (Coleman & Rubens, 1987 Group, 1986). The administration of chemotherapy may be complicated by the liver's role in both cytotoxic drug activation, as for cyclophosphamide (Bagley et al., 1973), and metabolism, as with doxorubicin (Benjamin et al., 1974). Moreover, although anthracyclines are the most active single agents in patients with breast cancer (Steiner et al., 1983), toxicity can be severe in patients with impaired liver function and reduced hepatic drug clearance (Benjamin et al., 1974).Epirubicin (4'-epidoxorubicin) is a new anthracycline, structurally related to doxorubicin and with similar activity in patients with advanced breast cancer (Brambilla et al., 1986). It is eliminated more rapidly than doxorubicin (Camaggi et al., 1988) and, at equimolar doses, is less toxic than doxorubicin (Brambilla et al., 1986). We report our experience of the efficacy and toxicity of epirubicin in patients with breast cancer and liver metastases who have abnormal liver biochemistry.Patients received a low dose of epirubicin on a weekly schedule, with the aim of giving a high dose intensity whilst minimising toxicity. Patients and methodsThirty-six patients with histologically proven breast cancer, progressive liver metastases and abnormal liver biochemistry were entered into this phase II study.