The combination of radiotherapy, adjuvant chemotherapy (cyclophosphamide-doxorubicin-ftorafur) and tamoxifen in stage II breast cancer. Long-term follow-up results of a randomised trial

Abstract

Summary Two hundred patients with node positive stage II breast cancer were randomised to four groups after radical mastectomy and axillary evacuation: (1) Postoperative radiotherapy, (2) Adjuvant chemotherapy with eight courses of CAFt (cyclophosphamide 500 mg m-2 + doxorubicin 40 mg/m-2 + ftorafur 20 mg kg-' orally day 1-14) every fourth week, (3) Postoperative radiotherapy and adjuvant chemotherapy and (4) postoperative radiation, adjuvant chemotherapy and tamoxifen 40 mg daily for 2 years.Thirty-two per cent of the patients discontinued treatment due to GI-toxicity, while 26% required dose reductions due to leukopenia. Radiation pneumonitis was more frequent after the combination of postoperative radiotherapy with chemotherapy. There was a better relapse-free survival in the groups receiving chemotherapy compared to radiotherapy alone (P = 0.05), which was highly significant in a multivariate Cox analysis (P = 0.004). No significant survival differences were seen. Tamoxifen had no clear overall effect but there were better relapse-free (P = 0.04) and overall (P = 0.004) survival with tamoxifen in estrogen receptor positive patients, while estrogen receptor negative patients had a somewhat poorer survival (P = 0.07) after tamoxifen.Local control was better (NS) after the combination (93%) radiotherapy and chemotherapy compared to either treatment alone (76% with radiotherapy and 74% with chemotherapy at 5 years).

The use of a combination of tamoxifen and doxorubicin synergistically to induce cell cycle arrest in BT483 cells by down-regulating CDK1, CDK2 and cyclin D expression

“…Ahmann et al, reported that combined chemohormonal therapy with Tam, Dox and cyclophosphamide resulted in a higher objective response rate and a long median survival in patients with ER-positive tumors [24]. Similarly, another study found that the combination of radiotherapy, Dox and Tam seemed to improve both relapse-free and overall survival in ER-positive tumors [5]. The results of this study tend to support the findings of the two earlier with respect to the synergistic effect on cell survival in ER-positive breast cancers, but not in ER-negative breast cancers.…”

“…It is classified as an anticancer anthracycline antibiotic and is commonly used in the treatment of multiple cancers, including bladder cancer, breast cancer, ovarian cancer, lung cancer and gastric cancer [1][2][3][4]. However, several randomized clinical studies have included this drug in adjuvant regimens, possibly because of a fear of long-term cardiotoxicity [5]. Tam is a nonsteroidal selective estrogen receptor modulator that is widely used in the treatment of hormone-dependent breast cancers.…”

Postmastectomy Radiotherapy of the Chest Wall

“…This irradiation technique was designed for treating the whole chest wall and electron energies between 4 and 15 MeV were used, according to the minimal thickness of the chest wall (skin-surface to lung). Higher incidences of symptomatic radiation pneumonitis have also been reported in series in which a photon "hockey-stick" field was used to treat the internal mammary lymph nodes concurrently with chemotherapy [2]. Symptomatic pneumonitis occurred in only one of 164 irradiated patients in the British Columbia trial, in which chemotherapy and postmastectomy radiotherapy were given sequentially [30].…”

Clinical Approach to the Compromised Host with Fever and Pulmonary Infiltrates

“…Finally, there appears to be individual variability in susceptibility to radiation injury, as there are several reports of severe pneumonitis developing after relatively small doses of radiation. 109,110,[118][119][120][121][122][123] One might question whether such increased susceptibility is related pathogenetically to the uncommon occurrence of extensive radiation pneumonitis beyond the radiation field. A trivial explanation for these events is that they result from technical errors involving radiation port placement.…”