Serious Hematologic Complications Following Erlotinib Treatment

Background: Erlotinib is an oral, small-molecule targeting therapy which inhibits epidermal growth factor tyrosine kinase receptors. Erlotinib has been administered for the treatment of advanced pancreatic cancer and non-small cell lung cancer. Patients and Methods: In the present report, unusual hematologic complications were detected after erlotinib was administered as second-line monotherapy in pretreated patients with advanced non-small cell lung cancer. Four patients pre-treated with cisplatin or its analog-based combinations, were evaluated. Erlotinib was given at a dose of 150 mg daily. In cases of intolerable adverse reactions, the dose was either reduced to 100 mg daily or treatment was interrupted for a maximum of two weeks. Results: Serious hematologic toxicity (or complications) developed in these 4 patients after 4-8.5 months of treatment. Two patients developed leukemias (AML, CML) and two, myelodysplastic syndrome. Conclusion: Whether or not these hematologic complications were related to erlotinib treatment is comprehensively discussed. Erlotinib is an oral, small-molecule targeting therapy which inhibits the epidermal growth factor receptor (EGFR) of tyrosine kinase, blocking signal transduction pathways implicated in the proliferation and survival of cancer cells (1). EGFR is associated with cellular processes leading to tumorigenesis (2, 3). Data exist concerning erlotinib administration for malignant tumors, mainly pancreatic cancer, in combination with another cytotoxic agent and also for non-small cell lung cancer (NSCLC) in a large number of patients as second-line treatment (4). Erlotinib has provided a survival benefit for advanced NSCLC patients (5, 6). Survival benefit was even shown in several subsets of NSCLC patients such as patients with squamous cell carcinoma, smokers and males, where gefitinib did not appear to be active (5). Serious adverse reactions are uncommon. The most common side-effects are skin rash and serious grade 3-4 anorexia and then fatigue, vomiting and stomatitis which were reported to be <1%. Grade 3-4 diarrhea was also <1% (6). The present report involves erlotinib monotherapy in pretreated patients with advanced NSCLC. Case Reports Case 1. A 67-year-old male patient was histologically diagnosed with inoperable, stage IIIB adenocarcinoma, with pleura infiltration and pleura infusion. This patient was treated with cisplatin 80 mg/m 2 -gemcitabine 1 gr/m 2