Acute and Subacute Toxicity Associated with Concurrent Adjuvant Radiation Therapy and Paclitaxel in Primary Breast Cancer Therapy

Abstract

The purpose of this study was to describe the toxicity of concurrent standard dose adjuvant radiation therapy (RT) and paclitaxel in a series of patients receiving primary breast cancer therapy. From June 1998 to April 1999, 20 patients with breast cancer received concurrent adjuvant radiation and paclitaxel. There were 16 patients (80%) with American Joint Committee on Cancer (AJCC) stage II disease and 4 with stage III disease. Eighteen patients, 12 postmastectomy and 6 breast conservation, were treated with definitive surgery followed by concurrent RT and paclitaxel. Two received concurrent neoadjuvant radiation and paclitaxel. All patients received a doxorubicin-containing combination prior to radiation and paclitaxel. RT was delivered concurrently with paclitaxel after the completion of all doxorubicin therapy, with all patients receiving at least two cycles of paclitaxel (175 mg/m2) every 3 weeks during RT. Toxicity was graded weekly according to Radiation Therapy Oncology Group criteria. Thirteen patients (65%) developed grade 2 or higher cutaneous toxicity. In the postmastectomy group, 6 of 12 patients (50%) developed grade 2 cutaneous toxicity, and 4 of 12 patients (33%) developed grade 3. RT was discontinued in 1 and placed on hold in 3 of these patients. In the breast-conservation group, 2 of 6 patients (33%) developed grade 3 toxicity. In the neoadjuvant group, 1 of 2 patients (50%) developed grade 3 toxicity. Four patients (20%) developed radiation pneumonitis, 2 of 12 (17%) in the postmastectomy group and 2 of 6 (33%) in the breast conservation group, with 2 requiring hospitalization and 1 a diagnostic open-lung biopsy. In this group of patients, standard dose concurrent radiation and paclitaxel resulted in a high incidence of cutaneous and pulmonary toxicity. Concurrent radiation and paclitaxel with these doses and schedule should be approached cautiously until further studies documenting its safety are completed.

NK105, a paclitaxel-incorporating micellar nanoparticle, is a more potent radiosensitising agent compared to free paclitaxel

“…The severity of lung fibrosis did not differ significantly among the test groups either. Although some clinical trials reported an increased incidence of pneumonitis and esophagitis following combined PTX therapy with radiation (Taghian et al, 2001;Hanna et al, 2002;Chen and Okunieff, 2004), others reported no influence on the incidence of such adverse effects (Ellerbroek et al, 2003;Yu et al, 2003). Several clinical trials and in vivo experiments have discussed the subject, however, no definitive conclusion has been arrived at Choy et al, 1998;Yu et al, 2004;Kao et al, 2005).…”

“…Lung toxicities often result in lung fibrosis, necessitating change of the treatment method and causing much distress or even death of the patients (Penney and Rubin, 1977;Early Breast Cancer Trialists' Collaborative Group, 2000;Lind et al, 2002). Some clinical trials actually reported an increased incidence of pneumonitis following combined PTX therapy with radiation in patients with breast or lung cancer (Taghian et al, 2001;Hanna et al, 2002;Chen and Okunieff, 2004).…”

Paclitaxel-induced Interstitial Pneumonia after Drug-eluting Stent Implantation: Report of a Fatal Case

“…Paclitaxel-induced interstitial pneumonia occurs in approximately 1% of treated patients (5,6). Although many of these side effects appear to be schedule and dose dependant (7,8), several reports have indicated that pulmonary toxicity is not in this category, and that paclitaxel may trigger pulmonary allergic responses (8)(9)(10)(11) (6,(12)(13)(14)(15) …”

Clinical practice guidelines for the care and treatment of breast cancer: 16. Locoregional post-mastectomy radiotherapy

“…91,92 Tamoxifen and various chemotherapy agents have been associated with increased pulmonary side effects with PMRT. [93][94][95][96] Among 1624 women treated with radiotherapy to the breast or chest wall alone or locoregional radiotherapy to the breast or chest wall plus lymph nodes, pneumonitis developed in 3% of patients treated with locoregional radiotherapy and chemotherapy compared with 0.5% in all other patients (p = 0.0001) (level V evidence). 91 Radiation pneumonitis occurred in 8.8% of patients receiving concurrent locoregional radiotherapy and chemotherapy, as compared with 1.3% of patients receiving sequential treatment (p = 0.002).…”

“…103 Several retrospective series have implicated the anthracyclines and taxanes as drugs associated with increased risks of toxicities to normal structures, including the skin, soft tissues, lung and heart, when delivered concurrently with radiotherapy (level V evidence). 46,93,94 The optimal sequencing of PMRT and adjuvant endocrine therapy is also unclear. A retrospective analysis of 84 postmenopausal women treated in the prospective randomized Danish study suggested a higher risk of pulmonary fibrosis among women who received concurrent tamoxifen and PMRT than among women who did not receive tamoxifen (OR 2.9, p = 0.007) (level V evidence).…”