title: 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.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Kaplan Comprehensive Cancer Center, New York University School of Medicine, New York, NY, USA. silvia.formenti@med.nyu.edu
authors.forename: Silvia C
authors.initials: SC
authors.lastname: Formenti
authors.forename: Matthew
authors.initials: M
authors.lastname: Volm
authors.forename: Kristin A
authors.initials: KA
authors.lastname: Skinner
authors.forename: Darcy
authors.initials: D
authors.lastname: Spicer
authors.forename: Deidre
authors.initials: D
authors.lastname: Cohen
authors.forename: Edith
authors.initials: E
authors.lastname: Perez
authors.forename: Anna C
authors.initials: AC
authors.lastname: Bettini
authors.forename: Susan
authors.initials: S
authors.lastname: Groshen
authors.forename: Conway
authors.initials: C
authors.lastname: Gee
authors.forename: Barbara
authors.initials: B
authors.lastname: Florentine
authors.forename: Michael
authors.initials: M
authors.lastname: Press
authors.forename: Peter
authors.initials: P
authors.lastname: Danenberg
authors.forename: Franco
authors.initials: F
authors.lastname: Muggia
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000009:adverse effects / Q000627:therapeutic use*; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D015411:Mastectomy, Modified Radical; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000627:therapeutic use*; D011182:Postoperative Care; D011183:Postoperative Complications; D011300:Preoperative Care; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D011878:Radiotherapy; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D011838:Radiation-Sensitizing Agents; D004317:Doxorubicin; D017239:Paclitaxel