Rajesh Sehgal

Bevacizumab and irinotecan therapy in glioblastoma multiforme: a series of 13 cases.

OBJECT Endothelial proliferation has been recognized as a marker of high-grade or aggressive glioma. Bevacizumab is a humanized immunoglobulin G1 monoclonal antibody to vascular endothelial growth factor that has been shown to have activity in malignant gliomas when combined with irinotecan. The authors report on a case series of 13 patients with recurrent heavily pretreated malignant glioma that was treated with the combination of bevacizumab and irinotecan. METHODS Standard therapy with primary resection followed by adjuvant chemotherapy and radiation had failed in all patients. The median number of therapies applied, including initial surgery, was 5 (range 3-7 therapies). Nine patients were started on bevacizumab at a dose of 5 mg/m2 every 2 weeks. Four patients received bevacizumab at a dose of 10 mg/m2; irinotecan was given at a dose of 125 mg/m2 every week for 3 weeks. RESULTS Of the 13 treated patients, 10 (77%) had a radiologically demonstrated partial response and 3 (23%) had stable disease. Six patients (46%) had a clinical response. The median time to disease progression while on treatment was 24 weeks. The median overall survival was 27 weeks. The disease progressed in 8 patients, despite an initial response. Five patients are still responding to therapy. Six of the 8 patients whose disease progressed have died. Bevacizumab was discontinued in 2 patients because of nonfatal intracranial bleeding. CONCLUSIONS The combination of bevacizumab and irinotecan is safe and has excellent activity even in this relapsed, heavily pretreated population of patients with high-grade malignant glioma, most of whom would not be candidates for clinical trials.

Survival Outcomes in Pregnancy Associated Breast Cancer: A Retrospective Case Control Study

Abstract:  Pregnancy‐associated breast cancer (PABC) has been defined as breast cancer diagnosed during pregnancy or within one year of delivery. It is believed that after adjusting for age and stage, the 5‐year survival rates are the same in both pregnant and nonpregnant women. We conducted a retrospective case‐control study among patients treated at our institution between 1990 and 2005 to compare the 5‐year survival outcomes for PABC with women treated for breast cancer who were not pregnant. Overall survival (OS) and disease‐free survival (DFS) were estimated by the Kaplan–Meier method, and log rank tests were used to assess the associations between OS, DFS and pregnancy status, HER‐2 status, ER/PR status, and family history. The median age was 33 years (range 24–42) for both groups. Twenty‐two (55%) patients with PABC were ER/PR receptor positive compared with 20 (50%) for the controls. Ninety percent of patients with PABC received chemotherapy compared with 87.5% in the nonpregnant group. 91.5% of patients with PABC had breast‐conserving surgery and 8.5% had mastectomies compared with 86% and 14%, respectively, for the control group. The median OS was 4.9 years in the PABC group compared with 6 years for the controls (p = 0.02). The median DFS was 2.7 years for the PABC group compared with 5.1 years for the controls (p = 0.01). The most common site of relapse was bone for the PABC group (27%) and local recurrence (33%) for the controls. Univariate analysis revealed that OS and DFS were associated with pregnancy status, family history, ER/PR status, and stage. After adjusting for age and stage, PABC patients had higher risk of both death (p = 0.01) and recurrence (p = 0.02) compared with nonpregnant controls. Women with PABC had significantly shorter OS and DFS compared with nonpregnant age and stage‐matched controls.

Gemtuzumab ozogamicin as first-line treatment in patients aged 70 years or older with acute myeloid leukemia

Elderly patients with acute myeloid leukemia (AML) are generally unable to withstand the rigors of intensive induction chemotherapy and its attendant complications. Gemtuzumab ozogamicin (GO) is an immunoconjugate that had demonstrated activity in recurrent AML.

Mitoxantrone and etoposide in patients with newly diagnosed acute myeloid leukemia with persistent leukemia after a course of therapy with cytarabine and idarubicin.

The most effective regimen for patients with acute myeloid leukemia (AML) who do not achieve complete remission (CR) after one course of cytarabine and an anthracycline has not been extensively studied. We evaluated restrospectively the efficacy, toxicity, and prognostic factors for the achievement of CR following mitoxantrone and etoposide in 74 patients with newly diagnosed AML who did not respond to one course of therapy with cytarabine and idarubicin. CR was achieved in 39% of patients; 14% died of infectious complications; no grade 3 or 4 hepatic toxicities were observed. Median duration of overall survival was 9.0 months (95% CI 5.8–14.9 months). The median duration of relapse-free survival was 11.0 months (95% CI: 9.0–19.3 months). A lower CR rate was associated with unfavorable risk status at diagnosis and higher percent blasts. Our data suggest that the combination of etoposide and mitoxantrone is an effective second-course therapy in patients with newly diagnosed AML.

Multiple Myeloma and Other Hematological Malignancies of Bone

Multiple Myeloma (MM) is a hematologic malignancy characterized by neoplastic clonal proliferation of plasma cells typically resulting in the presence of a monoclonal immunoglobulin (Ig) present in the blood and/or urine. MM is responsible for 1% of malignant diseases, and comprises 10% of all hematologic malignancies, making it the second most common hematologic malignancy in adults, second to only Non-Hodgkins lymphoma. The estimated annual incidence of MM is approximately 4 per 100,000 in Caucasians and 8 per 100,000 in African-Americans with a projected 19,900 new cases to be diagnosed in 2007 in the United States and approximately 10,790 deaths due to myeloma to occur [46]. The incidence is lower in the Asian population. The incidence of MM increases with age with median age at diagnosis being 68 years, with a greater incidence of the disease in males as compare to females.

Survival differences in colorectal cancer (CRC) on the basis of race: University of Pittsburgh Medical Center (UPMC) experience

4041 Background: CRC has higher 5-yr survival in whites (W) (65%) as compared to African Americans (AA) (55%). Our study was aimed to detect factors that might affect survival in these two groups at UPMC. Methods: Of 2,494 patients (pts) diagnosed with CRC at UPMC from 1994–2005, complete data (age, sex, disease status, tumor characteristics, treatment & overall survival) were available for 1,800 pts (181 AA & 1619 W). Results: Average age was 68 yrs in AA vs 69 in W. Pts with stage I, II, III, & IV in AA vs W were 22% vs 18%, 27% vs 34%, 32% vs 29% & 19% vs19%, respectively. Tumor grade differentiation in AA vs W was well (WD) in 2% vs 3%, moderate (MD) in 83% vs 76 %, poor (PD) in 14%vs 20% and undifferentiated (UD) in 1% vs 1% of pts, respectively. Median (M) time from diagnosis to starting treatment was 8 days in AA vs 11 in W. M number (no.) of lymph nodes (LN) examined were 12 in AA vs 14 in W. Overall M survival time (MST) was 49 months (m) in AA vs 67 m in W (p=0.09). MST for stage II+III pts was ...