Afatinib With Pembrolizumab for Treatment of Patients With Locally Advanced/Metastatic Squamous Cell Carcinoma of the Lung: The LUX-Lung IO/KEYNOTE 497 Study Protocol.

BACKGROUND: Afatinib is a selective, irreversible ErbB family blocker that has shown survival benefit in lung squamous-cell carcinoma (SCC) patients. Pembrolizumab, a humanized immunoglobulin G4 monoclonal antibody to the programmed cell death 1 (PD-1) receptor, has also shown survival benefit in lung SCC. Concurrent inhibition of the PD-1 and epidermal growth factor receptor (EGFR) pathways represents a rational approach to improve responses and delay the onset of treatment resistance in lung SCC. TRIAL DESIGN: This phase II, open-label, single-arm study (NCT03157089) is designed to assess the efficacy and safety of afatinib in combination with pembrolizumab in patients with stage IIIB/IV lung SCC that has progressed during/after first-line platinum-based chemotherapy. Eligible patients must have ≥1 target lesion (as per Response Evaluation Criteria in Solid Tumors version 1.1) and must have not received previous immune checkpoint inhibitor/EGFR-targeted therapy. The recommended phase II dose (RP2D) and safety profile will be determined during a safety run-in with oral afatinib (starting dose, 40 mg/d) with intravenous pembrolizumab (200 mg every 3 weeks). In the main study, all patients will receive afatinib at the RP2D with pembrolizumab until disease progression, unacceptable toxicity, or for up to 35 cycles. The primary end point is objective response (complete + partial response). Other end points include disease control, duration of objective response, progression-free survival, overall survival, tumor shrinkage, RP2D, and pharmacokinetics. Exploratory biomarker analysis will be performed. This study is being conducted in the United States, Spain, France, South Korea, and Turkey. Enrollment commenced in September 2017, with a target of 50 to 62 patients.

Amrubicin and carboplatin with pegfilgrastim in patients with extensive stage small cell lung cancer: A phase II trial of the Sarah Cannon Oncology Research Consortium.

PURPOSE: First-line treatment for patients with extensive-stage small cell lung cancer (SCLC) includes treatment with platinum-based combination chemotherapy. Amrubicin is a synthetic anthracycline with single-agent activity in relapsed/refractory SCLC. In an attempt to improve treatment efficacy, we evaluated amrubicin/carboplatin as first-line therapy for extensive-stage SCLC. PATIENTS AND METHODS: In this multicenter phase II trial, patients received amrubicin (30 mg/m2 daily on Days 1, 2, and 3) and carboplatin (AUC = 5 on Day 1); cycles were repeated every 21 days for 4 cycles. Pegfilgrastim (6 mg subcutaneously) was administered on Day 4 of all cycles. Overall survival (OS) proportion at 1 year was the primary endpoint. The target 1-year OS rate was 47%, an improvement of 35% from historical results with carboplatin/etoposide. RESULTS: Eighty patients received study treatment, and 62% completed the planned 4 courses. The overall response rate was 74% (13% complete responses). The 1-year survival rate was 38% (95% CI: 25, 50). The median survival was 10 months. Myelosuppression was severe but manageable. CONCLUSIONS: The combination of amrubicin/carboplatin was an active first-line treatment for extensive stage SCLC, but showed no indication of increased efficacy compared to standard treatments. Severe myelosuppression was common with this regimen, in spite of prophylactic pegfilgrastim. These results are consistent with those of other trials in showing no role for amrubicin in the first-line treatment of SCLC.

EGFR Genotyping of Matched Urine, Plasma, and Tumor Tissue in Patients With Non-Small-Cell Lung Cancer Treated With Rociletinib, an EGFR Tyrosine Kinase Inhibitor.

PURPOSE: Liquid biopsies represent an attractive alternative to tissue biopsies, particularly rebiopsies, in determining patient eligibility for targeted therapies. Clinical utility of urine genotyping, however, has not been explored extensively. We evaluated epidermal growth factor receptor (EGFR) T790M detection in matched urine, plasma, and tissue and the clinical outcomes of patients with advanced non-small-cell lung cancer treated with rociletinib. METHODS: Tissue (n = 540), plasma (n = 482), and urine (n = 213) were collected from evaluable patients enrolled in TIGER-X, a phase I/II study. Genotyping was performed by therascreen EGFR testing in tissue, BEAMing in plasma, and a quantitative short footprint assay (Trovera) in urine, which was used to further examine discordant samples. RESULTS: Positive percent agreement with tissue T790M results was similar for urine (82%; 142 of 173) and plasma (81%; 313 of 387) genotyping. Urine and plasma together identified more patients who were T790M positive (92%) than tissue alone (83%) among matched samples (n = 177). The ability to identify mutations in plasma was strongly associated with M stage (P < .001); rate of T790M detection for patients with M1a/M0 disease increased from 54% for plasma alone to 85% when urine and plasma were both examined. Objective response rates of patients who were T790M positive were comparable between tumor (34%), plasma (32%), and urine (37%). CONCLUSION: Clinical response to rociletinib was comparable irrespective of whether T790M status was identified by liquid or tissue biopsy. Combined, urine and plasma identified a higher percentage of patients who were T790M positive than tumor genotyping alone and improved detection of T790M, particularly in the absence of distant metastases. These findings support the noninvasive analysis of urine and plasma before tumor rebiopsy when assessing T790M status.

First-Line Carboplatin, Pemetrexed, and Panitumumab in Patients with Advanced Non-Squamous KRAS Wild Type (WT) Non-Small-Cell Lung Cancer (NSCLC).

BACKGROUND: We added panitumumab to standard combination chemotherapy as first-line treatment for patients with advanced KRAS WT non-squamous NSCLC. METHODS: Patients received panitumumab 9 mg/kg IV, pemetrexed 500 mg/m2 IV, and carboplatin AUC = 6 IV every 21 days. After 6 cycles, maintenance therapy with panitumumab and pemetrexed was administered every 21 days until progressive disease or unacceptable toxicity. RESULTS: 29 of 66 patients (44%) had objective responses. The median TTP was 6 months; median overall survival (OS) was 17 months. Panitumumab increased treatment-related toxicity, notably skin rash. CONCLUSIONS: The addition of panitumumab increased toxicity, and had no discernible impact on efficacy.

Metastatic Anaplastic Lymphoma Kinase-1 (ALK-1)-Rearranged Inflammatory Myofibroblastic Sarcoma to the Brain with Leptomeningeal Involvement: Favorable Response to Serial ALK Inhibitors: A Case Report.

BACKGROUND ALK gene rearrangements as oncogenic drivers have been described in many cancers, including inflammatory myofibroblastic sarcoma (IMS). The first-generation ALK inhibitor was limited in its ability to cross the blood-brain-barrier to treat brain metastasis. Drug-resistance invariably develops over time in ALK-rearranged tumors, which leads to disease progression. The newer generations of ALK inhibitors are designed to have higher potency in ALK inhibition and improved CNS penetration. CASE REPORT We report a rare case of pulmonary IMS with ALK-1 gene rearrangement and multiple brain metastases as initial presentation. After the primary lung tumor and the larger brain metastases were resected, control of residual CNS disease and subsequent progression and CNS spread was achieved with favorable clinical response by all three generations of ALK inhibitors. CONCLUSIONS ALK inhibitors may be an effective therapy for this rare and unusual form of ALK-1-rearranged cancer, even in the presence of multifocal CNS metastases with leptomeningeal involvement.

Winning the battle, losing the war: the noncurative "curative" resection for stage I adenocarcinoma of the lung.

BACKGROUND: Understanding recurrence of surgically "cured" stage I adenocarcinoma of the lung is important given expected benefits of adjuvant therapy for advanced disease. Therefore, this study characterizes cancer recurrence and its risks, assesses survival after recurrence, and contextualizes overall survival and its risks. METHODS: From 1991 to 2001, 285 patients underwent resection of stage I adenocarcinoma (pathologic) of the lung. They were followed cross-sectionally for evidence of cancer recurrence (mean follow-up 7.7 ± 4.3 years). Risk factors for recurrence and all-cause mortality were sought among demographic, medical history, cancer pathology, and surgical procedure data. RESULTS: Cancer recurred in 99 patients. Freedom from recurrence was 92%, 72%, and 57% at 1, 5, and 10 years. Two phases of risk were found: an early hazard phase and an essentially constant late phase after 5 years, with recurrences equally distributed. Early recurrence was associated with larger tumor size in patients who did not undergo mediastinal lymphadenectomy (p = 0.004). Late recurrence was more common in patients with higher pack-years of smoking (p = 0.007). Survival after recurrence was 40% and 17% at 1 and 5 years. Overall survival (65% and 40% at 5 and 10 years) depended not only on variables related to cancer recurrence, but also those of vitality (older age, pulmonary dysfunction, postpneumonectomy state). CONCLUSIONS: Stage I adenocarcinoma of the lung recurs. Identifying high-risk patients will simplify decision making for adjuvant therapy and surveillance. Thorough mediastinal lymphadenectomy dissociates tumor size as a predictor of survival and may itself provide an important survival benefit.

Combinations of DNA methyltransferase and histone deacetylase inhibitors induce DNA damage in small cell lung cancer cells: correlation of resistance with IFN-stimulated gene expression.

Because epigenetic inhibitors can reduce cancer cell proliferation, we tested the hypothesis that concurrent inhibition of histone acetylation and DNA methylation could synergistically reduce the viability of small cell lung cancer (SCLC) cells. Sub-IC(50) concentrations of the DNA methyltransferase (DNMT) inhibitor decitabine (5-AZA-dC) and the histone deacetylase (HDAC) inhibitors (LBH589 or MGCD0103) synergistically reduced the proliferation of five of nine SCLC cell lines. Loss of viability of sensitive SCLC cells did not correlate with the inhibition of either DNMT1 or HDACs, suggesting nonepigenetic mechanisms for synergy between these two classes of epigenetic modulators. Because combinations of 5-AZA-dC and HDAC inhibitors had marginal effects on the apoptosis index, Comet assay was undertaken to assess DNA damage. MGCD0103 and 5AZA-dC cotreatment augmented DNA damage in SCLC cells, resulting in increased tail length and moment in Comet assays by 24 hours in sensitive cell lines (P < 0.01). Consistent with augmented DNA damage, combination of a DNMT and HDAC inhibitor markedly increased the levels of phospho-H2A.X in sensitive cells but not in resistant ones. Comparison of basal gene expression between resistant and sensitive cells identified markedly higher basal expression of IFN-stimulated genes in the resistant cell lines, suggesting that IFN-stimulated gene expression may determine SCLC cell sensitivity to epigenetic modulators or other DNA damaging agents.

Gender, race, and survival: a study in non-small-cell lung cancer brain metastases patients utilizing the radiation therapy oncology group recursive partitioning analysis classification.

PURPOSE: To explore whether gender and race influence survival in non-small-cell lung cancer (NSCLC) in patients with brain metastases, using our large single-institution brain tumor database and the Radiation Therapy Oncology Group recursive partitioning analysis (RPA) brain metastases classification. METHODS AND MATERIALS: A retrospective review of a single-institution brain metastasis database for the interval January 1982 to September 2004 yielded 835 NSCLC patients with brain metastases for analysis. Patient subsets based on combinations of gender, race, and RPA class were then analyzed for survival differences. RESULTS: Median follow-up was 5.4 months (range, 0-122.9 months). There were 485 male patients (M) (58.4%) and 346 female patients (F) (41.6%). Of the 828 evaluable patients (99%), 143 (17%) were black/African American (B) and 685 (83%) were white/Caucasian (W). Median survival time (MST) from time of brain metastasis diagnosis for all patients was 5.8 months. Median survival time by gender (F vs. M) and race (W vs. B) was 6.3 months vs. 5.5 months (p = 0.013) and 6.0 months vs. 5.2 months (p = 0.08), respectively. For patients stratified by RPA class, gender, and race, MST significantly favored BFs over BMs in Class II: 11.2 months vs. 4.6 months (p = 0.021). On multivariable analysis, significant variables were gender (p = 0.041, relative risk [RR] 0.83) and RPA class (p < 0.0001, RR 0.28 for I vs. III; p < 0.0001, RR 0.51 for II vs. III) but not race. CONCLUSIONS: Gender significantly influences NSCLC brain metastasis survival. Race trended to significance in overall survival but was not significant on multivariable analysis. Multivariable analysis identified gender and RPA classification as significant variables with respect to survival.

Metastatic sarcomatoid renal cell carcinoma treated with vascular endothelial growth factor-targeted therapy.

PURPOSE: Metastatic renal cell carcinoma (mRCC) with sarcomatoid differentiation is an aggressive disease that is associated with poor outcomes to chemotherapy or immunotherapy. The utility of vascular endothelial growth factor (VEGF)-targeted therapy in patients with this disease is unknown. PATIENTS AND METHODS: Patients who had mRCC with sarcomatoid features in the primary tumor and who were treated with VEGF-targeted therapy were retrospectively identified. Pathology slides were reviewed to determine the percentage of sarcomatoid differentiation. Objective response rate, percentage of tumor burden shrinkage, progression-free survival (PFS), and overall survival (OS) were determined. RESULTS: Forty-three patients who had sarcomatoid mRCC were identified. The median percentage of sarcomatoid features was 14% (range, 3% to 90%). Patients were treated with either sunitinib (49%), sorafenib (28%), bevacizumab (19%), or sunitinib plus bevacizumab (5%). Partial responses were observed in eight patients (19%); 21 patients (49%) had stable disease; and 14 patients (33%) had progressive disease as their best response. Partial responses were limited to patients who had underlying clear-cell histology and less than 20% sarcomatoid elements. Median tumor shrinkage was -2% (range, -85% to 127%), and 53% achieved some degree of tumor shrinkage on therapy. Median PFS and OS were estimated to be 5.3 months and 11.8 months, respectively. CONCLUSION: Patients who have mRCC and sarcomatoid differentiation can demonstrate objective responses and tumor shrinkage to VEGF-targeted therapy. Patients who have clear-cell histology and a lower percentage of sarcomatoid differentiation may have better outcomes with VEGF-targeted therapy.

Utility of positron emission tomography compared with mediastinoscopy for delineating involved lymph nodes in stage III lung cancer: insights for radiotherapy planning from a surgical cohort.

PURPOSE: Mediastinoscopy is routinely carried out on the majority of nonmetastatic, non-small-cell lung cancer (NSCLC) patients in our institution. We used the results of mediastinoscopy from a Stage III NSCLC cohort to assess the reliability of positron emission tomography (PET) scans at identifying involved mediastinal lymph nodes (MLN) when used during radiotherapy planning. METHODS AND MATERIALS: Mediastinoscopy was the gold standard. Characteristics of PET were calculated for nodal sensitivity. To compare the impact on contouring, theoretical nodal targets (NTs) containing involved MLNs were generated using PET and mediastinoscopy. We determined whether the NT derived from PET (NT-P) was equivalent to, greater than, or less than that seen with the mediastinoscopy (NT-M). RESULTS: Data for 122 patients with Stage III NSCLC, treated between 2000 and 2004, were analyzed. After exclusions, 87 patients with Stage III disease by mediastinoscopy were analyzed. Overall PET sensitivity was 61% and positive predictive value was 94%. Of the 87 patients, 33 (38%) had no abnormal MLN findings by PET. Of 36 Stage IIIA cancer patients, 18 (50%) had NT-P equivalent to NT-M, 10 (28%) had smaller NT-Ps, and 8 (22%) had larger NT-Ps compared with NT-Ms. Of 18 Stage IIIB cancer patients, NTs were equivalent in 6 (34%); in 1 patient (5%) NT-P was larger than the corresponding NT-M, and in 11 (61%) smaller than the corresponding NT-M. CONCLUSIONS: In this study PET had modest sensitivity to detect MLN involvement and underestimated the extent of involved nodes for target definition. The role of PET in mediastinal contouring needs to be evaluated prospectively and ideally correlated with a pathology standard.

Phase II study of gemcitabine and cisplatin in patients with previously untreated extensive stage small cell lung cancer: Southwest Oncology Group Study 9718.

BACKGROUND: This phase II study (S9718) evaluated the antineoplastic activity and tolerability of the combination of gemcitabine and cisplatin in previously untreated patients with extensive stage small cell lung cancer (ES-SCLC). METHODS: Chemonaive patients with ES-SCLC, received gemcitabine 1250 mg/m intravenously (IV) over 30 minutes on days 1 and 8 and cisplatin 75 mg/m IV over 30 to 60 minutes on day 1. Treatments were repeated every 21 days for a maximum of six cycles. RESULTS: A total of 88 patients were enrolled in the study; seven patients were not eligible and one did not receive treatment; 80 patients were fully assessable for survival, response, and toxicity. Objective response was observed in 42 patients (53%; 95% confidence interval [CI]: 41%-64%) with two patients (3%; 95% CI: 0%-8%) achieving a complete response. Median PFS was 5 months (CI, 4.2-5.9 months), and median overall survival was 8.8 months (95% CI: 7.8-9.5 months). The 1- and 2-year survival rates were 27.5% (95% CI: 17.7%-37.3%) and 4% (95% CI: 0%-8%), respectively. The most common toxicity was neutropenia. Grade 3 and 4 neutropenia was noted in 17 (21%) and 17 (21%) patients, respectively. Two patients developed febrile neutropenia, with subsequent full recovery. Twenty-one patients (23%) developed grade 3 thrombocytopenia. Grade 4 thrombocytopenia was seen in only one patient. The most common nonhematologic toxicities included grade 3 and 4 vomiting in 12 (21%) patients and fatigue in nine (10%) patients. Two patients (3%) died of respiratory infections while on treatment. CONCLUSION: The combination of gemcitabine and cisplatin is an active and reasonably well tolerated regimen for the treatment of ES-SCLC. It does not appear to offer any compelling advantages over other commonly used two drug regimens in this disease.

Validation of the RTOG recursive partitioning analysis (RPA) classification for small-cell lung cancer-only brain metastases.

PURPOSE: The Radiation Therapy Oncology Group (RTOG) developed a prognostic classification based on a recursive partitioning analysis (RPA) of patient pretreatment characteristics from three completed brain metastases randomized trials. Clinical trials for patients with brain metastases generally exclude small-cell lung cancer (SCLC) cases. We hypothesize that the RPA classes are valid in the setting of SCLC brain metastases. METHODS AND MATERIALS: A retrospective review of 154 SCLC patients with brain metastases treated between April 1983 and May 2005 was performed. RPA criteria used for class assignment were Karnofsky performance status (KPS), primary tumor status (PT), presence of extracranial metastases (ED), and age. RESULTS: Median survival was 4.9 months, with 4 patients (2.6%) alive at analysis. Median follow-up was 4.7 months (range, 0.3-40.3 months). Median age was 65 (range, 42-85 years). Median KPS was 70 (range, 40-100). Number of patients with controlled PT and no ED was 20 (13%) and with ED, 27 (18%); without controlled PT and ED, 34 (22%) and with ED, 73 (47%). RPA class distribution was: Class I: 8 (5%); Class II: 96 (62%); Class III: 51 (33%). Median survivals (in months) by RPA class were: Class I: 8.6; Class II: 4.2; Class III: 2.3 (p = 0.0023). CONCLUSIONS: Survivals for SCLC-only brain metastases replicate the results from the RTOG RPA classification. These classes are therefore valid for brain metastases from SCLC, support the inclusion of SCLC patients in future brain metastases trials, and may also serve as a basis for historical comparisons.

Phase II study of lenalidomide in patients with metastatic renal cell carcinoma.

BACKGROUND: Lenalidomide (LEN) is a structural and functional analogue of thalidomide that has demonstrated enhanced immunomodulatory properties and a more favorable toxicity profile. A Phase II, open-label study of LEN in patients with metastatic renal cell carcinoma (RCC) was conducted to determine its safety and clinical activity. METHODS: Patients with metastatic RCC received LEN orally at a dose of 25 mg daily for the first 21 days of a 28-day cycle. The primary endpoint was the objective response rate. Time to treatment failure, safety, and survival were secondary endpoints. RESULTS: In total, 28 patients participated in the trial and were included in the current analysis. Three of 28 patients (11%) demonstrated partial responses and continued to be progression-free for >15 months. Eleven patients (39%) had stable disease that lasted >3 months, including 8 patients who had tumor shrinkage. In total, 6 patients (21%) remained on the trial, and 5 additional patients continued to be followed for survival. The median follow-up for those 11 patients was 13.5 months (range, 8.3-17.0 months). The median survival had not been reached at the time of the current report. Serious adverse events included fatigue (11%), skin toxicity (11%), and neutropenia (36%). CONCLUSIONS: LEN demonstrated an antitumor effect in metastatic RCC, as evidenced by durable partial responses. LEN toxicities were manageable. Further studies will be required to assess the overall activity of LEN in patients with metastatic RCC.

Phenoxodiol: isoflavone analog with antineoplastic activity.

Phenoxodiol, a synthetic analog of the plant isoflavone genistein, represents a new generation of oncology drugs acting as multiple signal transduction regulators. Phenoxodiol exerts its effect mainly by the induction of apoptosis through multiple mechanisms resulting in degradation of antiapoptotic proteins, with increased levels being linked to chemoresistance in tumor cells. Preclinical studies with this agent showed promising anticancer activity leading to a potential role in the treatment of a wide range of solid and hematologic cancers. Early clinical studies, especially in chemotherapy-resistant ovarian cancer, showed minimal toxicity with minor antitumor activity. Hormone-refractory prostate cancer is another promising area in which phenoxodiol is being actively tested. Studies are ongoing to define the optimal use of this novel anticancer agent.

Malignant acanthosis nigricans, tripe palms and the sign of Leser-Tre'lat, a hint to the diagnosis of early stage ovarian cancer: a case report and review of the literature.

BACKGROUND: Malignant acanthosis nigricans is a mucocutaneous eruption associated with internal malignancies. Tripe palms refers to a characteristic velvety thickening of the palms, with exaggeration of normal skin markings. The sign of Leser-Tre'lat is the presence of multiple seborrheic keratoses and scattered skin tags caused by a malignancy. We are reporting the first case of ovarian cancer in association with three coexisting cutaneous paraneoplastic dermatosis. CASE: A 52-year-old female presented with skin manifestation consistent with MAN, TP and the sign of Leser-Tre'lat. Patient underwent extensive work up and was discovered to have stage I, high grade adenocarcinoma of the ovary. Skin manifestations gradually recovered after initiation of chemotherapy. CONCLUSION: The presence of acanthosis nigricans in conjunction with tripe palms and the sign of Leser-Tre'lat are highly suggestive of an internal malignancy and necessitate an extensive investigation in order to discover the underlying malignancy.

Validation and extension of the Memorial Sloan-Kettering prognostic factors model for survival in patients with previously untreated metastatic renal cell carcinoma.

PURPOSE: To validate the Motzer et al prognostic factors model for survival in patients with previously untreated metastatic renal cell carcinoma (RCC) and to identify additional independent prognostic factors. PATIENTS AND METHODS: Data were collected on 353 previously untreated metastatic RCC patients enrolled onto clinical trials between 1987 and 2002. RESULTS: Four of the five prognostic factors identified by Motzer were independent predictors of survival. In addition, prior radiotherapy and presence of hepatic, lung, and retroperitoneal nodal metastases were found to be independent prognostic factors. Using the number of metastatic sites as surrogate for individual sites (none or one v two or three sites), Motzer's definitions of risk groups were expanded to accommodate these two additional prognostic factors. Using this expanded criteria, favorable risk is defined as zero or one poor prognostic factor, intermediate risk is two poor prognostic factors, and poor risk is more than two poor prognostic factors. According to Motzer's definitions, 19% of patients were favorable risk, 70% were intermediate risk, and 11% were poor risk; median overall survival times for these groups were 28.6, 14.6, and 4.5 months, respectively (P < .0001). Using the expanded criteria, 37% of patients were favorable risk, 35% were intermediate risk, and 28% were poor risk; median overall survival times of these groups were 26.0, 14.4, and 7.3 months, respectively (P < .0001). CONCLUSION: These data validate the model described by Motzer et al. Additional independent prognostic factors identified were prior radiotherapy and sites of metastasis. Incorporation of these additional prognostic factors into the Motzer et al model can help better define favorable risk, intermediate risk, and poor risk patients.

Renal cell carcinoma (RCC) and telomerase activity: relationship to stage.

Limited information is available on the correlation of telomerase activity and the clinical and pathological characteristics, in patients with renal cell carcinoma (RCC). Telomerase repeat amplification protocol (TRAP) was used to measure telomerase activity in frozen RCC specimens from partial/radical nephrectomies performed between 1987 and 1991. Presence of tumor tissue was verified by a pathologist using hematoxylin and eosin stained sections. RNA was measured to ensure the presence of intact protein necessary for telomerase expression. Data on demographics, tumor type, and stage at presentation, local recurrence, distant metastasis, disease-free survival (DFS), and overall survival (OS) was collected, and telomerase activity was correlated with each of these variables. Forty-nine of 67 patients (73%) were telomerase positive (+ve). Gender and stage were the only variables that appeared to be associated with telomerase positivity. Tumors were telomerase +ve in 12/21 females (57 %) vs. 37/46 males (80%) (P = 0.07). Tumors were telomerase +ve in 85% of Stage IV, 76% of Stage III, and 70% of Stage I/II patients (P = 0.12). Five-year survival was 0% for Stage IV, 57% for Stage III, and 77% for Stage I/II patients (P < 0.001), DFS 54% for stage III and 84% for Stage I/II patients (P = 0.05). Telomerase activity, however, was not related to survival in either univariate or multivariate analysis. In patients with telomerase +ve tumors 5-year survival was 55%, and with telomerase -ve tumors 58% (P = 0.56). Stage was the only variable associated with OS or DFS in clear cell RCC patients. In patients with advanced disease, there is a high incidence of telomerase positivity was found, within this limited sample, however, no correlation with survival was found.

F-18 fluorodeoxyglucose positron emission tomography in the evaluation of distant metastases from renal cell carcinoma.

PURPOSE: We conducted a study to evaluate the role of F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) in the detection of distant metastases from renal cell carcinoma (RCC). MATERIALS AND METHODS: Twenty-four patients with histologically proven clear-cell RCC undergoing surgical evaluation for possible resection of recurrent disease were investigated. All patients had suspected distant metastases based on conventional anatomic imaging techniques (computed tomography and magnetic resonance imaging). A total of 36 distant metastatic sites were identified. Pathology for all sites was obtained by biopsy or after surgical resection. RESULTS: Histologically documented distant metastases from RCC were present in 33 sites (21 patients). Overall sensitivity, specificity, and positive predictive value of FDG-PET for the detection of distant metastases from RCC was 63.6% (21 of 33), 100% (three of three), and 100% (21 of 21), respectively. The mean size of distant metastases in patients with true-positive FDG-PET was 2.2 cm (95% CI, 1.7 to 2.6 cm) compared with 1.0 cm in patients with false-negative FDG-PET (95% CI, 0.7 to 1.4 cm; P =.001). CONCLUSION: FDG-PET is not a sensitive imaging modality for the evaluation of metastatic RCC and may not adequately characterize small metastatic lesions. However, positive FDG-PET is predictive for the presence of RCC in lesions imaged, may complement anatomic radiologic imaging modalities, and may alleviate the need for a biopsy in selected situations. A negative FDG-PET, however does not rule out active malignancy.

Paclitaxel in cancer therapy.

The last decade witnessed the introduction of exciting new chemotherapeutic agents. Among these, paclitaxel emerged as one of the most powerful compounds. Paclitaxel promotes the polymerisation of tubulin, thereby causing cell death by disrupting the normal microtubule dynamics required for cell division and vital interphase processes. Mechanisms of acquired resistance to paclitaxel include alterations of tubulin structure and the amplification of membrane phosphoglycoproteins that function as drug-efflux pumps. Toxicities associated with paclitaxel include hypersensitivity reaction, neurotoxicity and haematological toxicities. Toxicities may be both dose- and schedule-dependent. Paclitaxel has activity against a broad band of tumour types, including breast, ovarian, lung, head and neck cancers. Paclitaxel also has activity in other malignancies that are refractory to conventional chemotherapy, including previously-treated lymphoma and small cell lung cancers and oesophageal, gastric endometrial, bladder and germ cell tumours. Paclitaxel is also active against AIDS-associated Kaposi's sarcoma.

Acanthosis nigricans with endometrial carcinoma: case report and review of the literature.

BACKGROUND: Acanthosis nigricans is classified into benign and malignant forms on the basis of clinical associations. The main interest in acanthosis nigricans has been based on its association with malignancy because of the dramatic clinical appearance of the skin lesions and the usually rapidly fatal nature of the underlying disease. "Tripe palms" is a descriptive term of acanthosis nigricans of the palms. It more often is associated with internal malignancy. Most importantly, it often precedes the diagnosis of a new or recurrent tumor. Malignant acanthosis nigricans is most commonly associated with intra-abdominal malignancies. There are very few reports in the literature of malignant acanthosis nigricans associated with gynecological malignancies. Only five cases of endometrial carcinoma associated with acanthosis nigricans and/or tripe palms have been reported in the literature. CASE: A 69-year-old African-American female presented with skin changes consistent with the diagnosis of acanthosis nigricans and tripe palms. More than 14 months later she was found to have endometrial carcinoma. She subsequently underwent total abdominal hysterectomy and salpingo-oophorectomy followed by chemotherapy with paclitaxel and carboplatin. During treatment of the underlying malignancy the skin condition dramatically improved. CONCLUSION: Tripe palms can be associated with endometrial carcinoma and may be the first sign of malignancy. Malignant acanthosis nigricans may improve with treatment of the underlying malignancy. Patients who present with tripe palms may need to undergo workup to search for underlying malignancy.