Preoperative Twice-Weekly Paclitaxel With Concurrent Radiation Therapy Followed by Surgery and Postoperative Doxorubicin-Based Chemotherapy in Locally Advanced Breast Cancer: A Phase I/II Trial

• Published in: Journal of clinical oncology Vol. 21; no. 5; pp. 864 - 870
• Main Authors: FORMENTI, Silvia C, VOLM, Matthew, PRESS, Michael, DANENBERG, Peter, MUGGIA, Franco, SKINNER, Kristin A, SPICER, Darcy, COHEN, Deidre, PEREZ, Edith, BETTINI, Anna C, GROSHEN, Susan, GEE, Conway, FLORENTINE, Barbara
• Format: Journal Article
• Language: English
• Published: Baltimore, MD American Society of Clinical Oncology 01-03-2003; Lippincott Williams & Wilkins
• Subjects: Adult; Aged; Antineoplastic agents; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Breast Neoplasms - drug therapy; Breast Neoplasms - radiotherapy; Breast Neoplasms - surgery; Breast Neoplasms - therapy; Combined Modality Therapy; Combined treatments (chemotherapy of immunotherapy associated with an other treatment); Doxorubicin - adverse effects; Doxorubicin - therapeutic use; Feasibility Studies; Female; Humans; Mastectomy, Modified Radical; Medical sciences; Middle Aged; Neoplasm Staging; Paclitaxel - therapeutic use; Pharmacology. Drug treatments; Postoperative Care; Postoperative Complications; Preoperative Care; Radiation-Sensitizing Agents - therapeutic use; Radiotherapy; Treatment Outcome; Antineoplastic agent; Toxicity; Adjuvant treatment; Administration schedule; Doxorubicin; Neoadjuvant treatment; Isomerases; Surgery; Taxane derivatives; Phase II trial; Paclitaxel; Complication; Advanced stage; Mammary gland; Antimitotic; Human; Postoperative; DNA topoisomerase (ATP-hydrolysing); Enzyme; Treatment efficiency; Enzyme inhibitor; Malignant tumor; Radiotherapy; Mammary gland diseases; Antibiotic; Chemotherapy; Phase I trial; Anthracyclins; Combined treatment; Preoperative
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2003.06.132

Preoperative chemotherapy is the conventional primary treatment in locally advanced breast cancer (LABC). We investigated the safety and efficacy of primary twice-weekly paclitaxel and concurrent radiation (RT) before modified radical mastectomy followed by adjuvant doxorubicin-based chemotherapy.
Stage IIB (T3N0) to III LABC patients were eligible. Primary chemoradiation consisted of paclitaxel, 30 mg/m(2) delivered intravenously for 1 hour twice weekly for a total of 8 to 10 weeks, and concurrent RT (45 Gy at 1.8 Gy/fraction). Modified radical mastectomy was performed at least 2 weeks after completion of chemoradiation or on recovery of skin toxicity. Postoperatively, patients who responded to paclitaxel and RT received four cycles of doxorubicin/paclitaxel, whereas patients who did not respond received doxorubicin/cytoxan.
Forty-four patients were accrued. Toxicity from paclitaxel/RT included grade 3 skin desquamation (7%), hypersensitivity (2%), and stomatitis (2%). Postsurgery complications occurred in six patients (14%). The only grade 4 toxicity of postmastectomy chemotherapy was hematologic (10%). Grade 3 toxicities were leukopenia (24%), infection (22%), peripheral neuropathy (17%), arthralgia and pain (17%), stomatitis (12%), fatigue (10%), esophagitis (5%), and nausea (2%). Overall clinical response rate to preoperative paclitaxel and RT was 91%. Thirty-four percent of patients achieved a pathologic response in the mastectomy specimen: 16% pathologic complete responses (clearance of invasive cancer in the breast and axillary contents) and 18% pathologic partial responses (< 10 residual microscopic foci of invasive breast cancer).
Twice-weekly paclitaxel with concurrent RT is a feasible and effective primary treatment for LABC. Future studies should compare primary chemoradiation to chemotherapy in LABC.