After docetaxel was dropped in some people, the most common adverse effects were diarrhea (28.1%), upper respiratory tract infection (18.3%), rash (18.3%), headache (17.0%), fatigue (13.4%), swelling of nasal passages and throat (often due to catching the common cold) (17.0%), weakness (13.4%), itchiness (13.7%), joint pain (11.4%), nausea (12.7%), pain in an extremity (13.4%), back pain (12.1%) and cough (12.1%).In clinical trials of the neoadjuvant use of the combination, more than 50% of people had hair loss and loss of neutrophils.In both uses, more than 10% of people additionally experienced: loss of red blood cells, hypersensitivity or allergic reaction, infusion reactions, decreased appetite, insomnia, distortions in the sense of taste, inflammation of the mouth or lips, constipation, rashes, nail disease, and muscle pain. Pharmacology
The metabolism of pertuzumab has not been directly studied; in general antibodies are cleared principally by catabolism. The median clearance of pertuzumab was 0.235 liters/day and the median half-life was 18 days. Mechanism of action
HER2 is an extracellular receptor—a receptor tyrosine kinase - that when activated, sets off signal transduction through several pathways that stimulate cell proliferation and cell growth; if overexpressed it can cause uncontrollable growth. HER2 positive breast cancer is caused by ERBB2 gene amplification that results in overexpression of HER2 in approximately 15-30% of breast cancer tumors.Like many receptors HER2 normally combines another protein in order to function (a process called dimerization); it can bind with a second HER2 receptor (acting as a homodimer) and it can heterodimerize with a different receptor of the HER family.
It is also used in the same combination as a neoadjuvant (given to reduce the size of a tumor, prior to surgery or radiation) for HER2-positive early breast cancer; as of 2016 this use had not been shown to increase survival.As of 2016, pertuzumab has not been studied in people with a left ventricular ejection fraction value of ≤ 50% normal, a prior history of congestive heart failure, or conditions that could impair left ventricular function like uncontrolled hypertension, recent heart attacks, or serious cardiac arrhythmia. Caution should be used combining pertuzumab with an anthracycline. There is also no safety data available for use of pertuzumab in combination with doxorubicin.Women of child-bearing age should use contraception while taking pertuzumab; it may damage the fetus in pregnant women, and it may be secreted in breast milk. Adverse effects
In clinical trials of the three-agent combination therapy in metastatic breast cancer, adverse effects occurring in more than half the people taking it included diarrhea, hair loss, and loss of neutrophils; more than 10% of people experienced loss of neutrophils with fever, and loss of leukocytes.