Continuing chemotherapy or not after the induction treatment in advanced breast cancer patients: clinical outcomes and oncologists’ preferences

doi:10.1016/S0959-8049(02)00869-9

European Journal of Cancer

Volume 39, Issue 5, March 2003, Pages 614-621

https://doi.org/10.1016/S0959-8049(02)00869-9 Get rights and content

Abstract

The optimal duration of cytostatic treatment for metastatic breast cancer is still a matter of debate. Possible gain in the duration of remission has to be weighed against the side-effects of treatment. Our aim was to define the optimal duration of cyclophosphamide, methotrexate, 5-fluorouracil (CMF) treatment by studying the time to treatment failure, overall survival and using a Q-TWiST analysis. The treating physician's opinion was asked. The European Organization for Research and Treatment of Cancer (EORTC) Breast Cancer Group conducted a randomised trial in 204 non-progressing metastatic breast cancer patients after induction chemotherapy (CMF) to stop or continue treatment. Progression-free (PFS) and overall survival (OS) were studied. To gain more insight into the burden of treatment-related side-effects, Q-TWiST was analysed. In addition, we asked for oncologists’ preferences as patients are likely to be influenced by their physicians’ opinion. Continuation of CMF had a significantly longer time to treatment failure (TTF) 5.2 versus 3.5 months (P=0.011). There was no overall survival (OS) difference 14.0 versus 14.4 months (P=0.77). Mean quality-adjusted survival time was equal to 8.4 months for no further treatment and decreased to 7.9 months for continuation of CMF (95% Confidence Interval (CI) of difference equals 0.5±2.5 months). Almost half of the oncologists said they would favour continuous treatment for a 3-month gain in time to progression—a difference which was not found in this study. Based on these data, an interruption of chemotherapy (CMF), if this is the wish of the patient, is justified.

Introduction

In recent years, several studies have been undertaken to establish the optimal duration of cytostatic treatment in advanced metastatic breast cancer 1, 2, 3, 4, 5, 6, 7, 8. Survival has not been affected in a significant way 1, 2, 3, 4, 5, 6, 7, 8, but discussion on the optimal duration of treatment continues. The results of these trials pose a dilemma to clinicians and their patients with advanced breast cancer: a possible gain in time to progression has to be weighed against a loss in quality of life due to the side-effects of therapy.

From December 1985 until March 1992, the European Organization for Research and Treatment of Cancer (EORTC) Breast Cancer Group conducted a trial on the benefit of continuing cyclophosphamide, methotrexate, 5-fluorouracil (CMF) after induction with six cycles of CMF. As the opinions of clinicians play an important role in treatment proposals, it was decided to investigate the preferences of medical oncologists participating in this trial as well.

We report on the results of the randomised prospective trial comparing no further treatment with continuation of CMF until progression after induction chemotherapy (six cycles of CMF). Analyses were made for survival, progression-free survival (PFS) and quality-adjusted survival (Q-TWiST). The treatment preferences of medical oncologists involved in the trial are also presented.

Section snippets

Patients and characteristics

Eligible patients were postmenopausal women (1 year or more after their last period), younger than 71 years, with measurable and/or evaluable biopsy-proven advanced breast cancer, having received no chemotherapy for advanced disease. Previous adjuvant chemotherapy was allowed, provided the time between adjuvant therapy and development of metastases was at least 1 year.

World Health Organization (WHO) performance status had to be 2 or better, white blood cells (WBC) ⩾3×10⁹/l and platelets ⩾100×10⁹

Clinical evaluation

Between December 1985 and March 1992, 442 patients were registered for randomisation into the study by 18 institutions. A total of 204 patients were randomised (Table 2) either to continuation of CMF until progression or to no further treatment (Fig. 2). Of these, 20 were not eligible: 10 in the ‘continuous treatment’ arm and 10 in the ‘no further treatment’ arm. Characteristics of the randomised patients are shown in Table 3. With respect to overall response in the ‘continuous treatment’ and

Discussion

In this multicentre European study, the overall percentage of complete and partial remission is the same as in a comparable American study [3], conducted with cyclophosphamide, doxorubicin, 5-fluorouracil (CAF) chemotherapy. However, the percentage in remission is certainly lower than in other studies [17]. This might be related to patient selection, frequency of assessment or other factors as suggested for the American study. However, it may be that earlier studies were conducted in a more

Acknowledgements

The authors thank Dr. P. Bruning for carefully reading of the manuscript, Françoise Mignolet for data management and especially Anita de Wit for all her help in preparing the manuscript.

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Continuing chemotherapy or not after the induction treatment in advanced breast cancer patients: clinical outcomes and oncologists’ preferences

Abstract

Introduction

Section snippets

Patients and characteristics

Clinical evaluation

Discussion

Acknowledgements

Lancet

Eur. J. Cancer

Eur. J. Cancer

Hematol. Oncol. Clin. North Am.

Eur. J. Cancer

Eur. J. Cancer

Lancet

Improving the quality of life during chemotherapy for advanced breast cancer. A comparison of intermittent and continuous treatment strategies

N. Engl. J. Med.

Interrupted versus continuous chemotherapy in patients with metastatic breast cancer. The Piedmont Oncology Association

N. Engl. J. Med.