Gefitinib has shown modest activity in patients with recurrent non-small cell lung cancer (NSCLC) after platinum-based chemotherapy. However, the activity of gefitinib as first-line chemotherapy ...remains unclear, especially unknown in elderly patients. A multicenter phase II trial was conducted to evaluate the efficacy and tolerability of gefitinib for elderly patients with chemotherapy-naïve NSCLC.
Elderly chemotherapy-naïve patients with advanced NSCLC, ECOG PS of 0–2, and adequate organ functions received 250 mg/day of gefitinib. The primary objective of this study was to determine the objective response rate (RR). Secondary endpoints were tolerability, disease-related symptom using lung cancer subscale (LCS) in FACT-L, progression free survival (PFS) and overall survival (OS). We investigated mutation status of the epidermal growth factor receptor (EGFR) gene in cases with available tumor samples.
Fifty patients were enrolled, of whom 49 were eligible. Median age (range) was 80 (75–90) years. Thirty-two patients were female (65%) and 40 patients had adenocarcinoma (82%). The objective RR was 25% (CI 95%, 13–39). Median survival time was 10 months (CI 95%, 7–20) and 1-year survival rate was 50%. The most frequent adverse events were skin disorders (76%). Fifteen patients (30%) experienced toxicities ≥grade 3. There were four patients with possible interstitial lung disease including two treatment-related deaths. Symptom improvement rate using LCS was 49% at 4 weeks of gefitinib therapy. Tumor samples from 17 patients were analyzed for EGFR mutation status. EGFR mutations were detected in tumor tissues from 7 patients, of which 5 had partial responses (71%).
Gefitinib monotherapy is effective and relatively well tolerated in chemotherapy-naïve elderly patients with advanced NSCLC. Gefitinib has potential as a first-line therapeutic option in elderly patients with advanced NSCLC.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background
Various polymorphisms have been detected in the UDP‐glucuronosyltransferase 1A (
UGT1A
) gene, and
UGT1A1
*28 and
UGT1A1
*6 have important effects on the pharmacokinetics of irinotecan and ...the risk of severe toxicities during irinotecan therapy. This study was conducted to determine the maximum tolerated dose (MTD) of irinotecan chemotherapy according to the
UGT1A1
genotype in previously treated lung cancer patients with the
UGT1A1
*28 or
UGT1A1
*6 polymorphism.
Methods
The eligibility criteria were as follows: lung cancer patients that had previously been treated with anticancer agents other than irinotecan, possessed the
UGT1A1
*28 or
UGT1A1
*6 polymorphism (group A included *28/*28, *6/*6, and *28/*6, and group B included *28
/− and *6
/−), were aged ≤75 years old, had a performance score of 0–1, and exhibited adequate bone marrow function. The patients were scheduled to receive irinotecan on days 1, 8, 15, 22, 29, and 36.
Results
Four patients were enrolled in this trial. Two patients were determined to be ineligible. The remaining two patients, who belonged to group B, received an initial irinotecan dose of 60 mg/m2, but did not complete the planned treatment because of diarrhea and leukopenia. Thus, in group B patients, 60 mg/m2 was considered to be the MTD of irinotecan. The study was terminated in group A because of poor case recruitment.
Conclusions
The MTD of irinotecan for previously treated lung cancer patients that are heterozygous for the
UGT1A1
*
28 or
UGT1A1
*
6 gene polymorphism is 60 mg/m2.
Full text
Available for:
FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Abstract only
e13072
Background: Erlotinib is metabolized by cytochrome P450 enzymes to form a para-hydroxyaniline metabolite that is further metabolized to quinone-imine. Erlotinib is detoxified ...when it conjugates with sulfate or glucuronide. We recently demonstrated that patients who experienced severe erlotinib-induced hepatotoxicity had higher metabolic ratios of glucuronides than those who developed moderate toxicity; this finding indicates that glucuronidation could be saturated and high levels of reactive metabolites might be trigger of glutathione (GSH) depletion. Ophthalmic acid (OA), which is an analog of GSH, may be a useful biomarker for hepatotoxicity because it is a sensitive indicator of GSH depletion in animal model. GSH acts as an enzyme-catalyzed antioxidant when cells and organisms experience electrophilic stress that arises from metabolic processes. Here, we examined the association between plasma concentration of OA and hepatotoxicity in patients who were treated with erlotinib in Japanese patients. Methods: We assessed data from 26 patients with NSCLC who each received a 150 mg dose of erlotinib. Plasma concentrations of OA and erlotinib were measured at before treatment using the liquid chromatography-quadrupole mass spectrometer system. Results: All 26 patients experienced one or more erlotinib-induced adverse events. The most frequent erlotinib-induced adverse events were mild to moderate skin rashes and diarrhea. There seemed to be a relationship between the plasma concentration of erlotinib and the grades of skin rashes and diarrhea. Interestingly, OA was detected only in one patient who developed grade 4 hepatotoxicity, indicating that this patient, who had a higher level of OA (36.9 ng/mL) in plasma. In contrast, the other 25 patients, who did not develop hepatotoxicity, had no detectable OA in plasma. Thus, the plasma concentration of OA was not related to the plasma concentration of erlotinib nor to the grade of skin rash. Conclusions: OA might be useful as a predictive biomarker of hepatotoxicity if measured before starting erlotinib treatment. Larger studies are needed to investigate the association between OA levels and the development of severe hepatotoxicity.
Background. Bronchial foreign bodies are quite common in children and eldery people. There are few reports of bronchial foreign body caused by medicine in adolescence or late middle age. Case. A ...55-year-old man with diabetes mellitus and a 18-year history of hemodialysis for chronic renal failure consulted his home doctor because of prolonged cough. A bronchial foreign body was diagnosed and he was referred to our hospital. Chest radiograph and chest computed tomography revealed a high-density foreign body with a marked artifact in the truncus intermedius. The foreign body was suspected to be a button battery. We removed it by flexible bronchoscopy using basket type forceps. The removed foreign body appeared to be a tablet which was found to be lanthanum carbonate on confirmation of his prescribed medicines. Conclusion. We encountered a rare case of bronchial foreign body of lanthanum carbonate which had been initially suspected to be a button battery. Chewing this tablet is important to optimize its efficacy of phosphate adsorption and reduce potential risk of complications. Before prescribing lanthanum carbonate, it is necessary to educate patients about its use and consider patients' adaptability for this tablet.
Background
Various polymorphisms have been detected in the
UDP
‐glucuronosyltransferase 1
A
(
UGT1A
) gene, and
UGT1A1
*28
and
UGT1A1
*6
have important effects on the pharmacokinetics of irinotecan ...and the risk of severe toxicities during irinotecan therapy. This study was conducted to determine the maximum tolerated dose (
MTD
) of irinotecan chemotherapy according to the
UGT1A1
genotype in previously treated lung cancer patients with the
UGT1A1
*28
or
UGT1A1
*6
polymorphism.
Methods
The eligibility criteria were as follows: lung cancer patients that had previously been treated with anticancer agents other than irinotecan, possessed the
UGT1A1
*28
or
UGT1A1
*6
polymorphism (group
A
included
*28/*28, *6/*6
, and
*28/*6
, and group
B
included
*28
/−
and
*6
/−
), were aged ≤75 years old, had a performance score of 0–1, and exhibited adequate bone marrow function. The patients were scheduled to receive irinotecan on days 1, 8, 15, 22, 29, and 36.
Results
Four patients were enrolled in this trial. Two patients were determined to be ineligible. The remaining two patients, who belonged to group
B
, received an initial irinotecan dose of 60 mg/m
2
, but did not complete the planned treatment because of diarrhea and leukopenia. Thus, in group
B
patients, 60 mg/m
2
was considered to be the
MTD
of irinotecan. The study was terminated in group
A
because of poor case recruitment.
Conclusions
The
MTD
of irinotecan for previously treated lung cancer patients that are heterozygous for the
UGT1A1
*
28
or
UGT1A1
*
6
gene polymorphism is 60 mg/m
2
.
Full text
Available for:
FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
PDF
