Continuous infusional combination chemotherapy in inflammatory breast cancer: a phase II study

doi:10.1054/brst.1999.0158

The Breast

Volume 9, Issue 3, June 2000, Pages 149-155

https://doi.org/10.1054/brst.1999.0158 Get rights and content

Abstract

Despite the introduction of systemic chemotherapy, inflammatory breast cancer (IBC) remains a disease with a poor prognosis. We performed this phase II study to evaluate the efficacy of infusional chemotherapy as initial treatment in patients with IBC. Fifty-four patients with newly diagnosed IBC were offered infusional chemotherapy and 34 accepted. The schedule consisted of continuous infusional ECF (bolus epirubicin and cisplatin, substituted by carboplatin or cyclophosphamide in some patients) plus continuous 5-FU, given three weekly for six cycles. Following chemotherapy patients went on to have surgery and/or radiotherapy. The chemotherapy was well tolerated and resulted in an overall response rate of 79% with 35% of patients achieving a complete clinical response. The median response duration, time to progression and overall survival were 12 months (4–89+ months), 12 months (4–89+ months) and 23 months (7–89+ months), respectively. Patients had a 5 year disease free and overall survival of 11% and 29%, respectively. Infusional ECF is well tolerated and achieves a high clinical response rate in patients with IBC, but survival results do not appear to be superior to those achieved with conventional bolus chemotherapy schedules.

References (26)

WR Grace et al.
Inflammatory breast cancer
Surg Clin North Am
(1985)
J Attia-Sobol et al.
Treatment results, survival and prognostic factors in 109 inflammatory breast cancers: Univariate and multivariate analysis
Eur J Cancer
(1993)
T Palangie et al.
Prognostic factors in inflammatory breast cancer and therapeutic implications
Eur J Cancer
(1994)
W Thoms et al.
Multimodal treatment for inflammatory breast cancer
Int J Radiat Oncol Biol Phys
(1989)
J Fields et al.
Inflammatory carcinoma of the breast: Treatment results on 107 patients
Int J Radiat Oncol Biol Phys
(1989)
IA Jaiyesimi et al.
Inflammatory breast cancer: A review
J Clin Oncol
(1992)
F Lucas et al.
Inflammatory carcinoma of the breast
Cancer
(1978)
GN Hortobagyi et al.
Treatment of locally advanced and inflammatory breast cancer
NA Fastenberg et al.
Management of inflammatory carcinoma of the breast. A combined modality approach
Am J Clin Oncol
(1985)
PJ Cagnoni et al.
High dose chemotherapy with autologous hemopoietic progenitor-cell support as part of combined modality therapy in patients with inflammatory breast cancer
J Clin Oncol
(1998)

P Viens et al.

High-dose chemotherapy and haematopoietic stem cell transplantation for inflammatory breast cancer: pathologic response and outcome

Bone Marrow Transplant

(1998)

D Adkins et al.

Outcomes of high-dose chemotherapy and autologous stem-cell transplantation in stage IIIB inflammatory breast cancer

J Clin Oncol

(1999)

Cited by (11)

Neoadjuvant pegylated liposomal doxorubicin in combination with cisplatin and infusional fluoruracil (CCF) with and without endocrine therapy in locally advanced primary or recurrent breast cancer
2011, Breast
Citation Excerpt :
In the present study we investigated the activity of PLD in combination with cisplatin and infusional fluorouracil (CCF) as neoadjuvant therapy in a population of patients with locally advanced (including inflammatory) primary and recurrent breast cancer. The combination of cisplatin, infusional fluoruracil and epirubicin (ECF) has been extensively investigated showing substantial activity in the treatment of locally advanced operable and inoperable and metastatic breast cancer.10–13 In addition the combination of PLD and platinum derivates has been extensively investigated in ovarian cancer and has shown a benefit in terms of PFS as compared with platinum alone.14
To explore the activity of pegylated liposomal doxorubicin (PLD) as neoadjuvant therapy of breast cancer.
The combination of PLD with cisplatin and infusional fluorouracil (CCF) for 8 courses was investigated in patients with primary or recurrent T2-T4a-d N0-3 M0 breast cancer. Patients with ER and/or PgR ≥10% tumors also received letrozole (±triptorelin).
Forty patients entered the study. Four patients had recurrent tumors and 13 had cT4d tumors. Overall, clinical response rate was 77.5% whereas a pathological complete response (pCR) was obtained in 3 patients (7.7%), 4 when considering bilateral tumors. Noticeably 3 pCR were observed among the 10 patients with T4d ER positive tumors (33%). Eleven patients discontinued treatment before completion of the 8 planned courses.
Our results indicated that CCF yielded an appreciable rate of clinical responses in a series of very locally advanced tumors and an unusually high rate of pCR in T4d ER positive tumors, suggesting an enhanced cutaneous activity of PLD.
Phase II trial of combination of pegylated liposomal doxorubicin, cisplatin, and infusional 5-fluorouracil (CCF) plus trastuzumab as preoperative treatment for locally advanced and inflammatory breast cancer
2010, Clinical Breast Cancer
Citation Excerpt :
In the current study, we investigated the activity of the combination of PLD with cisplatin and infusional 5-fluorouracil (CCF) as preoperative treatment in a population of patients with locally advanced (including inflammatory) primary and recurrent HER2-positive breast cancer. The rationale for investigating this regimen was based on a number of studies showing substantial activity for the combination of epirubicin, cisplatin, and infusional 5-fluoruracil (ECF) in the treatment of locally advanced operable and inoperable and metastatic breast cancer.10–13 In addition, the combination of PLD and trastuzumab was proven active and safe in HER2-positive advanced breast cancer patients.14–16
Pegylated liposomal doxorubicin (PLD) was shown as active but less toxic compared to doxorubicin in advanced breast cancer. Given its low cardiotoxicity, the combination of PLD and trastuzumab appears most attractive in the treatment of human epidermal factor receptor 2 (HER2)-positive breast cancer. Patients and Methods: We investigated the activity of 8 courses of PLD in combination with cisplatin and infusional 5-fluorouracil (CCF) plus 3-week trastuzumab in patients with primary or recurrent cT2-T4 a-d, N0-3, M0 any estrogen receptor (ER), HER2-positive breast cancer. Patients with ER and/or progesterone receptor (PgR) ≥ 10% tumors received also letrozole (plus triptorelin if premenopausal). The principal endpoint was clinical response rate; secondary endpoints were the pathologic complete response rate (pCR) and the cardiac safety of the combination. Results: Thirty-two patients were enrolled in the study and all are evaluable for response and toxicity. Fifteen patients (47%) had ER-positive tumors, 15 patients and 2 patients had ER absent and ER poor tumors, respectively. Thirteen patients (41%) had inflammatory breast cancer (IBC) and 84% of patients had clinically positive nodes. A clinical response rate of 94% (95% CI, 79%-99%) and a pCR rate of 41% (95% CI, 24%-59%) were observed. Fifty-four percent of patients with IBC obtained a pCR. Eleven patients discontinued treatment before completing 8 courses as planned. No patient developed relevant cardiac toxicity. Conclusion: In this series of very locally advanced breast cancer, the combination of CCF and trastuzumab was very active obtaining an impressive rate of pCR, particularly in IBC, which merits further investigation in larger series.
Platinum-based chemotherapy in triple-negative breast cancer
2008, Annals of Oncology
Citation Excerpt :
In a phase II study, Garber et al. [9] have shown a pathological complete remission rate of 21% with neo-adjuvant cisplatin. For other reasons, we have considerable clinical experience with the use of platinum agents in patients with breast cancer in neo-adjuvant, adjuvant and metastatic settings [10–18]. In view of renewed interest in the use of platinum salts in patients with TN tumours, we have retrospectively reviewed patients within our database to assess outcome in those treated with platinum-based chemotherapy.
Experimental data suggest that triple-negative (TN) breast cancer may have increased sensitivity to platinum-based chemotherapy but clinical data are limited. We present our long-term results with platinum-based chemotherapy for TN breast cancer.
In all, 94 (17 TN), 79 (11 TN) and 155 (34 TN) patients receiving platinum-based chemotherapy in neo-adjuvant/adjuvant and advanced setting were included. Response rates and outcome were compared for TN tumours versus others.
Neo-adjuvant complete response rates were significantly higher for TN tumours (88%) than others (51%; P = 0.005). The 5-year overall survival (OS) for TN tumours following adjuvant/neo-adjuvant chemotherapy was 64% [95% confidence interval (CI) 44% to 79%] compared with 85% (95% CI 79% to 90%) for others. Five-year disease-free survival for TN tumours was 57% (95% CI 37% to 73%) compared with 72% (95% CI 64% to 78%) for others. For patients with advanced breast cancer, overall response rates were 41% for TN tumours and 31% for others (P = 0.3). Patients with TN tumours had a significantly prolonged progression-free survival of 6 months compared with 4 months for others (P = 0.05), though the OS was not significantly different between the two groups (11 versus 7 months).
Platinum-based chemotherapy achieves increased response rates for TN tumours, with a trend towards worse survival in early breast cancer through an improved survival in advanced disease. Prospective randomised trials are warranted.
A randomised phase II study of conventional versus accelerated infusional chemotherapy with granulocyte colony-stimulating factor support in advanced breast cancer
2002, Annals of Oncology
Citation Excerpt :
Accelerated chemotherapy schedules have also been applied in the neo-adjuvant and the high-risk adjuvant settings [8–10]. At the Royal Marsden Hospital, we developed a chemotherapy schedule of continuous infusional 5-fluorouracil (5-FU) with 3-weekly bolus epirubicin and cyclophosphamide (infusional ECF regimen), initially for patients with advanced disease [11], then inflammatory breast cancer [12] and then in patients with large operable disease [13]. The high activity of this regimen encouraged us to test whether this regimen could be accelerated to a 2-weekly schedule to decrease the time required for patients to complete their treatment programme and possibly also to improve efficacy.
Granulocyte colony-stimulating factor (G-CSF) allows cycles of conventional bolus chemotherapy to be accelerated with reduction in treatment time and a boost in dose intensity. Theoretically, this approach could be hazardous with infusional 5-fluorouracil (5-FU) chemotherapy, since G-CSF-stimulated neutrophil proliferation would be occurring in the face of continuous S-phase active 5-FU. We performed this phase II randomised study to compare the safety, tolerability and efficacy of conventional 3-weekly epirubicin, cyclophosphamide and continuous infusional 5-FU (infusional ECF) to an accelerated 2-weekly schedule with G-CSF support, in patients with advanced breast cancer.
Twenty-seven patients were randomised, with 14 in the accelerated arm. Patients received bolus epirubicin 60 mg/m² and cyclophosphamide 600 mg/m² every 3 weeks (conventional arm) or every 2 weeks (accelerated arm) and 5-FU 200 mg/m²/day continuous infusion throughout. G-CSF 300 µg/day s.c. on days 10–12 was given each accelerated cycle.
There were no treatment delays secondary to inadequate neutrophil or platelet recovery in either arm, with higher median day 1 neutrophil counts for each cycle in the accelerated arm compared with the conventional arm. Eighty-six per cent of the planned conventional chemotherapy cycles and 82% of the planned accelerated cycles were given. There were no major differences in toxicity between the arms, with the most common grade 3 toxicities being alopecia and stomatitis. Eight patients developed neutropenic sepsis (five in the accelerated arm and three in the conventional arm). Ten patients (77%) responded in the conventional arm and nine (64%) in the accelerated arm.
Accelerated infusional ECF with limited G-CSF support is a feasible and well-tolerated regimen with rapid haematological recovery. A 50% increase in relative dose intensity of epirubicin and cyclophosphamide is achieved, while overall treatment time is reduced by 33%.
Inflammatory breast cancer: A decade of experience
2016, Asia-Pacific Journal of Clinical Oncology
Dermal Drug Delivery for Cutaneous Malignancies: Literature at a Glance
2016, Journal of Pharmaceutical Innovation

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Original ArticleContinuous infusional combination chemotherapy in inflammatory breast cancer: a phase II study

Abstract

Surg Clin North Am

Eur J Cancer

Eur J Cancer

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Inflammatory breast cancer: A review

J Clin Oncol

Inflammatory carcinoma of the breast

Cancer

Treatment of locally advanced and inflammatory breast cancer

Management of inflammatory carcinoma of the breast. A combined modality approach

Am J Clin Oncol

High dose chemotherapy with autologous hemopoietic progenitor-cell support as part of combined modality therapy in patients with inflammatory breast cancer

J Clin Oncol

High-dose chemotherapy and haematopoietic stem cell transplantation for inflammatory breast cancer: pathologic response and outcome

Bone Marrow Transplant

Outcomes of high-dose chemotherapy and autologous stem-cell transplantation in stage IIIB inflammatory breast cancer

J Clin Oncol

Original Article
Continuous infusional combination chemotherapy in inflammatory breast cancer: a phase II study