Genetic polymorphisms and the efficacy and toxicity of cisplatin-based chemotherapy in ovarian cancer patients.

Platinum drugs are among the most active and widely used agents in the treatment of different cancers. However, the great individual variability in both outcome and toxicity of platinum chemotherapy requires the identification of genetic markers that can be used to screen patients before treatment. In this study, 21 polymorphisms in 10 genes, the protein activities of which may be addressed in different aspects of cisplatin metabolism, were tested for correlations with efficacy and toxicity of cisplatin-cyclophosphamide regimen in 104 ovarian cancer patients. The glutathione S-transferase P1 (GSTP1) Ile105Val polymorphism was strongly associated with progression-free survival (chi(2)=12.12, P=0.002). The allelic status of the GSTA1 -69 C>T polymorphism correlated with the overall survival: patients with T/T genotype survived longer than C/C carriers (P=0.044). Thrombocytopenia, anemia and neuropathy were less frequent among patients with the GSTM1-null or GSTM3 intron 6 AGG/AGG genotypes. Severe neutropenia was associated with the TP53 72 Pro/Pro, XPD 312 Asp/Asn and XRCC1 399 Arg/Arg genotypes. A higher risk of nephrotoxicity was noted for patients with the heterozygous ERCC1 19007 T/C and 8092 C/A genotypes. No correlations were found between genotypes and complete tumor responses.

Staging of recurrent and advanced lung cancer with 18F-FDG PET in a coincidence technique (hybrid PET).

The aim of this study was to evaluate [18F]fluorodeoxyglucose ( F-FDG) imaging of recurrent or inoperable lung cancer using a hybrid positron emission tomography (PET) device of the third generation. Examinations were compared with the results of conventional staging. Thirty-six patients suffering from recurrent or primarily inoperable lung cancer (29 men, seven women; age 64.8+/-12.0 years) were examined using hybrid PET (Marconi Axis gamma-PET ) 60 min after injection of 370 MBq F-FDG. The data obtained were reconstructed iteratively. All patients received a computed tomography (CT) scan using either the spiral or multislice technique. All lesions suspicious for primary or recurrent tumour were verified by biopsy; mediastinal lymph nodes were considered as malignant, when positive histology or a small axis diameter of greater than 1 cm measured with CT in addition to progression of clinical course was found. Distant metastases were diagnosed by CT and bone scintigraphy. Using hybrid PET all lesions showed a focally elevated glucose metabolism. Lymph node involvement of the ipsilateral peribronchial and hilar station (N1) was identified in 24/26 cases (92%), in 26/29 cases (90%) of ipsilateral central manifestation (N2) and in 11/13 (85%) cases of central contralateral or supraclavicular lymphatic infestation (N3). Pulmonary spread in hybrid PET was found in 4/8 cases (50%), whereas mainly lung metastases with a diameter of 1.5 cm and smaller were missed. Pleural involvement diagnosed by CT was verified in 4/5 patients. All four patients with bony metastases in conventional staging also presented with positive findings in hybrid PET (8/9 lesions). Concordance with conventional staging was found in 28/36 of patients (78%). In 4/36 patients (11%) unknown sites of tumour were detected leading to therapeutic consequences in three patients after radiological confirmation. Hybrid PET would have led to an understaging in four cases (11%), resulting theoretically in inefficient treatment in two patients. Hybrid PET for F-FDG imaging in the staging of recurrent or primarily inoperable lung cancer supplied equal (78%) or more information (11%) compared to conventional staging procedures. Using the information of hybrid PET alone, 11% of the patients would have been understaged. We conclude that hybrid PET has the potential for use as an additional staging tool in this subgroup of patients, providing supplementary information compared to conventional staging modalities.