Efficacy and safety of axitinib in patients with advanced non-small-cell lung cancer: results from a phase II study.

PURPOSE: This phase II study evaluated efficacy and safety of single-agent axitinib, an oral, potent, selective inhibitor of vascular endothelial growth factor receptors (VEGFR) -1, -2, and -3, in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: This was an open-label, single-arm, multicenter, phase II study with a Simon two-stage minimax design. Patients received a starting dose of axitinib 5 mg orally BID. The primary end point was Response Evaluation Criteria in Solid Tumors (RECIST) -defined objective response rate. Secondary end points included safety and tolerability, overall survival (OS), and progression-free survival (PFS). RESULTS: Thirty-two patients were enrolled, with a median age of 66.5 years. The majority of patients (75%) had adenocarcinoma. Nine patients (28%) had received no prior chemotherapy for metastatic disease, and 23 (72%) had received > or = one regimen. Three patients (9%) had a RECIST investigator-assessed, confirmed partial response (PR); disease control rate (PR + stable disease) was 41%. Median PFS was 4.9 months overall (95% CI, 3.6 to 7.0 months). Median OS was 14.8 months (95% CI, 10.7 months to not estimable) overall and 14.8 months (95% CI, 12.5 months to not estimable) in patients receiving first-line axitinib. One-year survival rates for patients with or without prior therapy for metastatic disease were 57% and 78%, respectively. Grade 3 treatment-related adverse events in > or = 5% of patients comprised fatigue (22%), hypertension (9%), and hyponatremia (9%). CONCLUSION: Axitinib demonstrated single-agent activity in patients with advanced NSCLC. Therapy was well tolerated with manageable toxicities. Further investigation of this VEGFR inhibitor in NSCLC is of interest.

Low socioeconomic status is a poor prognostic factor for survival in stage I nonsmall cell lung cancer and is independent of surgical treatment, race, and marital status.

BACKGROUND: Racial minorities exhibit poor survival with nonsmall cell lung cancer (NSCLC) that generally is attributed to low socioeconomic status (SES). In this study, the authors investigated the role of SES in this survival disparity among patients with stage I NSCLC. METHODS: A case-only analysis was performed on California Cancer Registry (CCR) data (1989-2003). Univariate survival analyses were performed using the Kaplan-Meier method. Multivariate survival analyses were performed using Cox proportional hazards ratios. RESULTS: In total, 19,702 incident cases of stage I NSCLC were analyzed. Low SES was identified more commonly in African-American and Hispanic patients and was associated significantly with men, unmarried status, stage IB disease, squamous cell histology, poorly differentiated tumors, fewer surgical resections performed, and less overall treatment received. Reasons for no surgery were associated strongly with low SES and unmarried status but not with race. In multivariate analysis, each incremental improvement in SES quintile was associated with statistically significant decreases in the hazard ratios (HRs) for death (second SES quintile [SES2] vs SES1: HR, 0.91; 95% confidence interval [95% CI], 0.85-0.98; SES3 vs SES1: HR, 0.90; 95% CI, 0.84-0.97; SES4 vs SES1: HR, 0.83; 95% CI, 0.77-0.89; SES5 vs SES1: HR, 0.78; 95% CI, 0.72-0.84; P(trend) < .0001). African-American or Hispanic race was not an independent poor prognostic factor for survival after adjustment for surgery, SES, and marital status. CONCLUSIONS: Low SES was an independent poor prognostic factor for survival in patients with stage I NSCLC and was independent of surgery, race, and marital status.

Survival improvements for advanced stage nonbronchioloalveolar carcinoma-type nonsmall cell lung cancer cases with ipsilateral intrapulmonary nodules.

BACKGROUND: Survival improvements have been demonstrated for patients with bronchioloalveolar (BAC) nonsmall cell lung cancer (NSCLC) with intrapulmonary satellite T4 nodules compared with other patients with stage IIIB disease, and for ipsilateral intrapulmonary M1 tumors versus contralateral or distant metastasis. However, it is not known whether these differences are observed in patients with non-BAC NSCLC. METHODS: A case-only analysis of the U.S. Surveillance, Epidemiology, and End Results (SEER) data (1999-2003) was conducted. Overall survival (OS) and lung cancer-specific survival (LCSS) univariate analyses were conducted using the Kaplan-Meier method. Multivariate survival analyses were performed using Cox proportional hazards ratios. RESULTS: A total of 27,435 incident cases of histologically confirmed, advanced stage NSCLC were identified. Cases with stage IIIB NSCLC due to multiple lesions in the same lobe (n = 633) had a significantly improved median OS (21 months) and LCSS (31 months) compared with other cases with stage IIIB NSCLC (n = 7695), with an OS of 7 months and an LCSS of 9 months (P < .0001 for both comparisons). Among cases with stage IV NSCLC, those with intrapulmonary nodules (n = 3010) had a significantly improved median OS (9 months) and LCSS (10 months) compared with those with distant metastasis (n = 16,097), with an OS of 4 months and an LCSS of 5 months (P < .0001 for both comparisons). These survival differences persisted after adjustment for age, sex, ethnicity, surgery, and radiotherapy. Among cases with stage IV NSCLC, those with ipsilateral intrapulmonary nodules (n = 1120) had improved OS (12 months) compared with those with bilateral intrapulmonary nodules (n = 1890), with an OS of 7 months (P < .0001). CONCLUSIONS: Cases with stage IIIB and IV NSCLC with ipsilateral intrapulmonary nodules were found to have improved survival outcomes compared with other cases with stage IIIB and IV disease. The results of the current study add additional support for modifications to the current NSCLC staging system.

Burkitt's lymphoma of the base of the tongue: a case report and review of the literature.

Burkitt's lymphoma is a highly aggressive, mature B cell non-Hodgkin's lymphoma that is rare outside Africa. We report a case of Burkitt's lymphoma presenting as a rapidly expanding tongue-base mass that caused airway obstruction in an 80-year-old Palestinian man living in California. According to our review of the literature, this is only the third reported case of Burkitt's lymphoma arising in the base of the tongue. We also discuss the incidence, epidemiology, genetics, prognosis, and treatment of this malignancy. Because Burkitt's lymphoma is one of the fastest-growing tumors in humans, rapid diagnosis and treatment are important. Treatment involves brief-duration, high-intensity chemotherapy and central nervous system prophylaxis. It is important for the otolaryngologist to recognize this disease and to understand the steps necessary to treat this aggressive tumor.

Prognostic factors for survival of stage I nonsmall cell lung cancer patients : a population-based analysis of 19,702 stage I patients in the California Cancer Registry from 1989 to 2003.

BACKGROUND: Platinum-based adjuvant chemotherapy in randomized trials has failed to provide a survival benefit in patients with resected stage I nonsmall cell lung cancer (NSCLC). Using data from the California Cancer Registry (CCR), we explored factors that had detrimental effects on survival in patients with stage I NSCLC to identify a subset of patients at high risk for disease recurrence and subsequent mortality. METHODS: Between 1989 and 2003, 19,702 incident cases of stage I NSCLC in the CCR were identified and subgrouped into stage IA and IB disease. Patient demographic factors, tumor characteristics, and treatment delivered were examined. Kaplan-Meier survival curves were calculated to estimate survival rates. Cox proportional-hazards ratios were used to identify independent prognostic factors for survival. RESULTS: Advanced age at diagnosis, male sex, low socioeconomic status (SES), nonsurgical treatment, and poor histologic grade (stage IA NSCLC: hazards ratio [HR], 1.13; 95% confidence interval [95% CI], 1.08-1.19; stage IB NSCLC: HR, 1.11; 95% CI, 1.07-1.16) were associated with increased mortality risk on multivariate analysis. Non-upper lobe tumor location (right middle lobe, right and left lower lobes) and tumor size > or =4 cm (vs <4 cm: HR, 1.23; 95% CI, 1.15-1.30) were additional factors that increased the risk of mortality among patients with stage IB disease. Bronchioloalveolar carcinoma and Asian ethnicity were associated with decreased mortality risk in stage I NSCLC. CONCLUSIONS: Stage I NSCLC with poorly differentiated histology and stage IB NSCLC with non-upper lobar tumor location or tumor size > or =4 cm carried an increased mortality risk.

Natural history of stage I non-small cell lung cancer: implications for early detection.

BACKGROUND: Concern has been raised that early detection of lung cancer may lead to the treatment of clinically indolent cancers. No population-based study has examined the natural history of patients with stage I NSCLC who receive no surgery, chemotherapy, or radiation therapy. Our hypothesis is that long-term survival in patients with untreated stage I non-small cell lung cancer (NSCLC) is uncommon. METHODS: A total of 101,844 incident cases of NSCLC in the California Cancer Center registry between 1989 and 2003 were analyzed; 19,702 patients had stage I disease, of whom 1,432 did not undergo surgical resection or receive treatment with chemotherapy or radiation. Five-year overall survival (OS) and lung cancer-specific survival were determined for this untreated group, for subsets of patients who were recommended but refused surgical resection, and for T1 tumors. RESULTS: Only 42 patients with untreated stage I NSCLC were alive 5 years after diagnosis. Five-year OS for untreated stage I NSCLC was 6% overall, 9% for T1 tumors, and 11% for patients who refused surgical resection. Five-year lung cancer-specific survival rates were 16%, 23%, and 22%, respectively. Among these untreated patients, median survival was 9 months overall, 13 months for patients with T1 disease, and 14 months for patients who refused surgical resection. CONCLUSION: Long-term survival with untreated stage I NSCLC is uncommon, and the vast majority of untreated patients die of lung cancer. Given that median survival is only 13 months in patients with T1 disease, surgical resection or other ablative therapies should not be delayed even in patients with small lung cancers.

Epidemiology of bronchioloalveolar carcinoma: improvement in survival after release of the 1999 WHO classification of lung tumors.

PURPOSE: Classification changes for bronchioloalveolar carcinoma (BAC) by the WHO in May 1999 narrowed its definition. This study was undertaken in an attempt to characterize the impact of these changes on the epidemiology of BAC. PATIENTS AND METHODS: This retrospective study involves data analysis from the population-based Cancer Surveillance Programs of three Southern California counties from 1995 to 2003. BAC cases diagnosed after May 1999 are compared with BAC cases before that time by clinicopathologic variables including survival. RESULTS: Incident cases (11,969) of non-small-cell lung cancer (NSCLC) were analyzed, including 626 cases of BAC (5.2%). Median overall survival (OS) for BAC patients diagnosed after May 1999 (> 53 months) was significantly improved over median OS for BAC patients before May 1999 (32 months; P = .012). This survival benefit remained after adjustment for sex, smoking status, and stage at presentation (hazard ratio for time of diagnosis before May 1999 compared with a diagnosis after May 1999 = 1.43; P = .015). Median OS for non-BAC NSCLC patients diagnosed before May 1999 (9 months) did not differ from the median OS of such patients afterwards (10 months; P = .09). CONCLUSION: This epidemiologic study is the first to demonstrate a survival advantage for BAC patients diagnosed after May 1999 compared with BAC patients diagnosed before this time-a finding that persists after adjustment for sex, smoking status, and stage at presentation. We believe that this observed survival benefit likely reflects changes in the revised 1999 WHO classification.