Overall 11% of patients experienced creatinine elevation, 1% severe. No discontinuations, dose reductions, or dose delays were
caused by renal toxicities.
Other Clinical Events
Nail changes (changes in pigmentation or discoloration of nail bed) have been reported. Edema occurred in 10% of patients; no
patients had severe edema. Dehydration and pyrexia were also reported.
6.2 Clinical Trials Experience in Non-Small Cell Lung Cancer
Adverse reactions were assessed in 514 ABRAXANE/carboplatin-treated patients and 524 paclitaxel injection/carboplatin-treated
patients receiving first-line systemic treatment for locally advanced (stage IIIB) or metastatic (IV) non-small cell lung cancer
(NSCLC) in a multicenter, randomized, open-label trial. ABRAXANE was administered as an intravenous infusion over 30 minutes
at a dose of 100 mg/m2 on Days 1, 8, and 15 of each 21-day cycle. Paclitaxel injection was administered as an intravenous infusion
over 3 hours at a dose of 200 mg/m2, following premedication. In both treatment arms carboplatin at a dose of AUC = 6 mg•min/mL
was administered intravenously on Day 1 of each 21-day cycle after completion of ABRAXANE/paclitaxel infusion.
The differences in paclitaxel dose and schedule between the two arms limit direct comparison of dose- and schedule-dependent
adverse reactions. Among patients evaluable for adverse reactions, the median age was 60 years, 75% were men, 81% were
White, 49% had adenocarcinoma, 43% had squamous cell lung cancer, 76% were ECOG PS 1. Patients in both treatment arms
received a median of 6 cycles of treatment.
The following common (≥ 10% incidence) adverse reactions were observed at a similar incidence in ABRAXANE plus carboplatin-treated and paclitaxel injection plus carboplatin-treated patients: alopecia 56%, nausea 27%, fatigue 25%, decreased appetite 17%,
asthenia 16%, constipation 16%, diarrhea 15%, vomiting 12%, dyspnea 12%, and rash 10% (incidence rates are for the
ABRAXANE plus carboplatin treatment group).
Table 7 provides the frequency and severity of laboratory-detected abnormalities which occurred with a difference of ≥ 5% for all
grades (1-4) or ≥ 2% for Grade 3-4 toxicity between ABRAXANE plus carboplatin-treated patients or paclitaxel injection plus
Table 7: Selected Hematologic Laboratory-Detected Abnormalities With a Difference of ≥ 5% for grades (1-4)
or ≥ 2% for Grade 3-4 Toxicity Between Treatment Groups
ABRAXANE (100 mg/m2 weekly)
Paclitaxel Injection (200 mg/m2 every 3 weeks)
Grades 1-4 (%) Grade 3-4 (%) Grades 1-4 (%) Grade 3-4 (%)
Anemia1,2 98 28 91 7
Neutropenia1,3 85 47 83 58
Thrombocytopenia1,3 68 18 55 9
1 508 patients assessed in ABRAXANE/carboplatin-treated group
2 514 patients assessed in paclitaxel injection/carboplatin-treated group
3 513 patients assessed in paclitaxel injection/carboplatin-treated group
Table 8 provides the frequency and severity of adverse reactions, which occurred with a difference of ≥ 5% for all grades (1-4) or
≥ 2% for Grade 3-4 between either treatment group for the 514 ABRAXANE plus carboplatin-treated patients compared with the 524
patients who received paclitaxel injection plus carboplatin.
Table 8: Selected Adverse Reactions with a Difference of ≥5% for All Grade Toxicity or ≥2% for Grade 3-4 Toxicity
Between Treatment Groups
MedDRA v 12.1
ABRAXANE (100 mg/m2 weekly)
Paclitaxel Injection (200 mg/m2
every 3 weeks) + carboplatin
Peripheralneuropathya 48 3 64 12
Edemaperipheral 10 0 4 <1
Epistaxis 7 0 2 0