title: Paclitaxel in metastatic breast cancer: a trial of two doses by a 3-hour infusion in patients with disease recurrence after prior therapy with anthracyclines.
abstract: BACKGROUND
  To date, anthracyclines are the most active drugs against breast tumors, and the taxane paclitaxel (Taxol) looks very promising. Both classes of drugs are affected by cellular multidrug-resistance mechanisms, and therefore their sequential use raises the possibility of clinical cross-resistance. It is therefore important to assess the activity of paclitaxel in patients with clinical resistance to anthracyclines.
  
  
  OBJECTIVE
  We assessed the safety and efficacy of paclitaxel administered by the logistically convenient 3-hour infusion to breast cancer patients who had disease progression within 12 months since prior therapy with anthracyclines.
  
  
  METHODS
  Fifty-one patients with metastatic breast cancer who had all relapsed or whose disease had progressed within 12 months from completion of an anthracycline-containing chemotherapy protocol (six receiving adjuvant therapy, 19 receiving neoadjuvant therapy, and 26 receiving treatment for metastatic disease) were enrolled in this phase II trial from June 1992 to May 1994. After medication to prevent type I acute hypersensitivity reactions, paclitaxel was given intravenously over 3 hours at 175 mg/m2 to the first 15 patients and at 225 mg/m2 to the next 36 patients. The median age was 50 years (range, 31-62 years), and the median Eastern Cooperative Oncology Group performance status was 0 (range, 0-2).
  
  
  RESULTS
  Patients received a median of five cycles (range, one to 11 cycles). After initial doses of 175 and 225 mg/m2, paclitaxel could be increased by 25 mg/m2 in 73% and 58% of cycles, respectively. Among 50 assessable patients, seven achieved a complete response and 12 achieved a partial response (response rate, 38% [95% confidence interval = 25%-53%]). The median duration of response was 7 months (range, 4-16 months), and the median time to disease progression for all patients was 5 months. Grade 4 neutropenia occurred in 3% of the cycles and in 12% of the patients and was never associated with fever and infection. Common toxic effects were myalgia and arthralgia (94% of the patients; 4% grade 3), peripheral neuropathy (92% of the patients; 8% grade 3), and alopecia (all patients). Pruritus and neuropathy were significantly more frequent and severe, respectively, with the higher dose (P < .01 by chi 2 test). Frequency and severity of other toxic effects were similar at either starting dose. Ten patients had symptoms of neuro-optic toxicity. Only one patient had a grade 2 hypersensitivity reaction.
  
  
  CONCLUSIONS
  Paclitaxel at starting doses of 175 and 225 mg/m2 given as a 3-hour infusion can safely be administered to, and is active in women whose disease has progressed after prior treatment with anthracyclines. There was evidence of increased toxicity at the higher dose but no suggestion of better efficacy.
  
  
  CONCLUSIONS
  Paclitaxel by a 3-hour infusion in combination with doxorubicin should be investigated in patients with metastatic breast cancer. Unless randomized trials demonstrate greater efficacy of the more toxic higher dose, it is suggested that a dose of 175-200 mg/m2 be administered with the 3-hour infusion schedule.
authors.affiliation: Division of Medical Oncology, Istituto Nazionale Tumori, Milan, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Gianni
authors.forename: E
authors.initials: E
authors.lastname: Munzone
authors.forename: G
authors.initials: G
authors.lastname: Capri
authors.forename: F
authors.initials: F
authors.lastname: Villani
authors.forename: C
authors.initials: C
authors.lastname: Spreafico
authors.forename: E
authors.initials: E
authors.lastname: Tarenzi
authors.forename: F
authors.initials: F
authors.lastname: Fulfaro
authors.forename: A
authors.initials: A
authors.lastname: Caraceni
authors.forename: C
authors.initials: C
authors.lastname: Martini
authors.forename: A
authors.initials: A
authors.lastname: Laffranchi
mesh_terms: D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000903:Antibiotics, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel