A 31-year-old patient, diagnosed in December 2009 with ductal carcinoma affecting the right breast, stage cT2N1M0, RE(+), PR(+), HER-2(+).
She received six cycles of docetaxel-trastuzumab in neoadjuvant therapy, undergoing left mastectomy with axillary dissection in June 2009.
He completed one year of treatment with trastuzumab, followed by monotherapy treatment for premenopausal patients (tamoxi 20 mg/24 h).
In October 2011, the patient was diagnosed with liver and bone metastases and was treated with nonpegylated liposomal doxorubicin-paclitaxel-trastuzumab.
Six cycles were completed with excellent response and tolerance, after which it was decided to continue trastuzumab in maintenance and hormonal maneuver (bilateral oophorectomy + letrozole).
In February 2013, the patient came to the emergency department with nocturnal seizures, which was repeated while being treated.
A cranial CT scan showed multiple lesions consistent with brain metastases.
During admission, anticonvulsant treatment consisting of valproic acid 500 mg/ 8h and levetiracetam 1,000 mg/12 h was prescribed, adding dexamethasone 8 mg/8 h (descending regimen) to the associated symptoms.
Ten sessions of holocraneal radiotherapy are programmed, during which the patient receives a total dose of 30 Gy.
Subsequently, treatment with lapatinib (1,250 mg/day) was initiated with uninterested capecitabine (1,500 mg/12 h) for days 1-14 of each cycle.
At this point, the results of the hematological/biochemical analysis are within normal limits, except for a discrete leukocytosis related to corticoid therapy.
The patients tolerance led to the treatment with capecitabine on day 18 of the first cycle due to poor digestive toxicity (diarrhoea grade 3), grade 2 asthenia, mucositis and oropharyngeal candidiasis.
The patient reported subsequent tremor related to manual activities, which led to a reduction in the dose of valproic acid (500 mg/ 12h).
Due to the persistence of tremor, plasma valproic levels are requested, resulting in a range (74.27 μg/mL, therapeutic range 50-100 μg/mL).
The capecitabine dose (1,300 mg/12 h) is reduced by 15% due to digestive toxicity and continued at reduced doses of lapatinib (1,000 mg/ day).
Three weeks later, the patient developed pain in the right hemiabdomen and subicteric skin dye.
Biochemical analysis revealed liver alterations: AST 95 U/L, ALT 134 U/L, total bilirubin (TBT) 3.1 mg/dL and direct bilirubin (DB) 2.2 mg/dL.
She also had alkaline phosphatase levels of 755 U/L, so it was decided to discontinue treatment.
One week after discontinuation of lapatinib, abdominal ultrasound is performed within normal limits, which together with a decrease in total bilirubin levels (2.32 mg/dL) and direct drug interaction (1.73 mg/dL).
Lapatinib is restarted, reducing the dose of valproic to 500 mg/day, resulting in digestive toxicity (nausea, vomiting, diarrheal stools) leading to immediate discontinuation.
Levels of serum transaminases and bilirubin remain elevated, indicating a new reduction in the dose of lapatin antiib (mg/day) with bilirubin. A decision is made to discontinue valproic acid, maintaining levetiracetam (1000).
One week after drug withdrawal, the patient experienced improvement, although tremor and laboratory abnormalities persist (GOT 52 U/L, GPT 71 U/L, BT 2 mg/dL and BD 1.59 mg/dL).
The pharmacist detects that medication is taken with food.
This could result in a marked increase in the oral bioavailability of lapatinib, therefore administration in the fasted state is recommended.
One week after modifying the regimen, the patient showed excellent tolerance to treatment, as well as transaminase and Bpat levels within the range of normal, allowing reintroduction of capecitabine (1/24300 mg q12h).
In successive revisions the patient maintains good general condition without relevant analytical alterations.
Our patient completed a total of 13 months of combined treatment until disease progression.
