ABSTRACT
The incidence of lung cancer is rising in pregnancy, which is diagnosed on stage III-IV in 98%. Almost half of these patients are non-smokers, who are associated with more epidermal growth factor receptor (EGFR)-mutated lung cancer. As cytotoxic chemotherapy is associated with poor outcome for mothers and prematurity for children this will probably lead to repeatedly question the use of EGFR-Tyrosine kinase inhibitors (TKI) (i.e. gefitinib and erlotinib) during pregnancy for EGFR-mutated lung cancer. EGFR-TKIs are recommended as the first line targeted therapy in case of advanced non small cell lung carcinoma (NSCLC) with an activating EGFR mutation but not recommended during pregnancy due to lack of data. We report clinical and pharmacological data for gefitinib during pregnancy in both the mother and fetus and resume the literature on the subject. A 33-year-old pregnant mother exhibited a disseminated EGFR-mutated lung carcinoma with respiratory distress at 26 weeks of pregnancy. Gefitinib administration was associated with rapid maternal respiratory improvement allowing a planned cesarian section on week 35, giving birth to a healthy baby (2575g) with regular development at 24 months of follow-up. The mother exhibited a progression-free survival of 42 weeks with an overall survival of 22 months. Gefitinib residual concentration was found in cord blood at 25.7ng/mL, confirming a transplacental transfer, but at only 20% of the maternal concentration measured at the same time (i.e. 127.1ng/mL). Gefitinib concentration in amniotic fluid, which represents chronic fetal exposure to the drug, was also 20% of the maternal residual concentration (16.9ng/mL) and reflected no fetal accumulation of the drug, despite both long half time elimination of gefitinib (i.e. 48h) and long time exposure (i.e. 55 days). This low transplacental transfer is an important report, as potential side effect toxicity on the fetus is likely correlated to gefitinib blood concentration.
Subject(s)
Antineoplastic Agents/adverse effects , Protein Kinase Inhibitors/adverse effects , Quinazolines/adverse effects , Adult , Antineoplastic Agents/administration & dosage , Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , ErbB Receptors/genetics , Erlotinib Hydrochloride , Fatal Outcome , Female , Humans , Lung Neoplasms/diagnosis , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Mutation , Pregnancy , Pregnancy Complications, Neoplastic/diagnosis , Pregnancy Complications, Neoplastic/drug therapy , Pregnancy Complications, Neoplastic/genetics , Pregnancy Outcome , Protein Kinase Inhibitors/administration & dosage , Quinazolines/administration & dosage , Radiography, Thoracic , Tomography Scanners, X-Ray ComputedABSTRACT
AIM OF THIS STUDY: To determine the prognosis of and prognostic factors for mesenteric node involvement in patients undergoing a bowel resection at the time of debulking surgery for primary treatment of advanced-stage ovarian cancer (ASOC). METHODS: A retrospective review of patients treated between 2005 and 2008 for ASOC and undergoing initial and interval debulking surgery with bowel resection (whatever the bowel segment). The characteristics and prognostic impact of mesenteric node involvement were studied. RESULTS: During the study period, 52 patients underwent debulking surgery for ASOC with bowel resection. Eighteen and 34 patients underwent initial or interval debulking surgery respectively. The most frequent site of the bowel resection was the rectosigmoid colon (38 patients; 73%) and 12 patients had resection of at least 2 intestinal segments. All patients had a complete macroscopic resection of peritoneal disease. Nineteen patients (37%) had mesenteric node involvement with a median of 4 involved nodes (range, 1-12). The degree of involvement of the intestinal wall and retroperitoneal node involvement (pelvic or para-aortic) had no impact on the risk of mesenteric node involvement. Overall survival and the location of recurrent disease were similar in patients with or without spread to mesenteric nodes. CONCLUSIONS: This study suggests that mesenteric node involvement is frequent in patients undergoing bowel resection in ASOC. Such spread does not appear to have an impact on patient survival. Modifying peroperative (particularly the extent of the mesocolon resection) or postoperative management is therefore unnecessary.
