[Show abstract][Hide abstract] ABSTRACT: This non-comparative phase II study (ClinicalTrials.gov: NCT00715208) evaluated bortezomib in place of vincristine in established rituximab-chemotherapy regimens in relapsed/refractory follicular (FL) or marginal zone lymphoma (MZL). Patients were allocated (physician/patient preference) to receive six 21-d cycles of: bortezomib 1·6 mg/m2 (days 1, 8), rituximab 375 mg/m2 (day 1), cyclophosphamide 1000 mg/m2 (day 1) and prednisone 100 mg (days 1–5; VR-CP; 47 FL, 1 MZL patients); or bortezomib, rituximab, prednisone per VR-CP, cyclophosphamide 750 mg/m2 and doxorubicin 50 mg/m2 (day 1; VR-CAP; 4 FL, 2 MZL, 1 chronic lymphocytic leukaemia patients). With VR-CP, the response rate was 77%, with a 27% complete response rate. After a median follow-up of 10·9 months, 40% of patients had relapsed/progressed or died. Median duration of response and progression-free survival was 21·9 and 14·9 months, respectively. Common drug-related grade ≥3 adverse events were neutropenia (25%), thrombocytopenia (6%) and lymphopenia (6%). Thirteen (27%) patients reported peripheral neuropathy (one grade 3). With VR-CAP, one FL patient achieved complete response and three FL and two MZL patients achieved partial responses. Three patients reported drug-related grade 1/2 peripheral neuropathy. Weekly bortezomib and rituximab represents an active, feasible treatment platform in FL. VR-CP was active and well tolerated in patients with relapsed/refractory FL.
British Journal of Haematology 07/2014; 166(6). DOI:10.1111/bjh.12991 · 4.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective:
Colorectal cancer (CRC) is among the most common cancers in Puerto Rico. Few studies have correlated clinical and pathological variables with the overall survival of CRC patients in Puerto Rico. We report the clinical and pathological characteristics of patients who underwent surgical resection at a community hospital in Puerto Rico.
Demographic and pathological variables of patients who underwent CRC surgery at Hospital del Maestro from 2006 through 2011 were reviewed. Descriptive statistics (mean, range, and frequency) and the Cox proportional hazards model were used to determine the influence of demographic and pathological variables on survival, after adjusting for age.
Two hundred and five CRC pathology reports were reviewed. Adenocarcinoma represented the most common pathology (202/205; 98.5%). Females represented 52% of the population (106/202) while males represented 48% (96/202). The median age was 71 years (30-96). The right colon was the most common site of presentation (49.7%; 100/201). Stage III was the most common stage at presentation. The presence of mucin, perineural or lymphatic invasion and tumor size were not related to decreased survival. Being male, having a higher stage at diagnosis, and having a moderately or poorly differentiated tumor were characteristics related to decreased survival.
This study provides information on clinical and pathological variables and their influence on the overall survival of CRC patients at a community hospital in Puerto Rico. Further research must be performed to identify potential disparities and their influence on the prognosis of this patients.
Puerto Rico health sciences journal 06/2014; 33(2):65-70. · 0.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This review will discuss the most recent literature regarding frontline therapy, treatment of patients not eligible for intensive chemotherapy, and novel agents for relapsed/refractory patients with mantle cell lymphoma (MCL).
Longer follow-up of previously studied intensive regimens still demonstrates encouraging results, but late relapses are still evident. Consolidation and maintenance strategies continue to be attractive options to be explored in this disease that is characterized by frequent relapses and short remissions. The combination of bendamustine-rituximab was demonstrated to be noninferior and less toxic to R-CHOP and should be considered the new standard of care for elderly patients. Multiple novel agents directed towards different molecular targets like BTK, mTOR, PI3K, HDAC, and BCL-2, involved in the pathogenesis of MCL have shown promising results.
Management of MCL still represents a challenge due to heterogeneity of the disease. As we approach the molecular era of oncology, future strategies should focus on combination of newer agents with known effective regimens to improve outcome.
Current opinion in oncology 09/2013; 25(6). DOI:10.1097/CCO.0000000000000010 · 4.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Vincristine sulfate liposome injection (VSLI; Marqibo(®) ; M) is active in relapsed and refractory lymphomas, and approved in the United States for relapsed and refractory adult acute lymphocytic leukaemia. We evaluated VSLI (2·0 mg/m(2) without dose cap) substituted for non-liposomal vincristine (VCR) in a cyclophosphamide, doxorubicin, vincristine, prednisone ± ritiximab (CHOP±R) regimen, creating CHMP±R in 72 untreated, aggressive non-Hodgkin lymphoma patients, including 60 with diffuse large B-cell lymphoma (DLBCL). The overall response rate was 96% (69/72) including complete response (CR) in 65 (90%) and unconfirmed CR in 2 (3%). Median progression-free survival (PFS) and overall survival (OS) were not reached at median follow-up of 8 and 10·2 years, respectively. The 5- and 10-year PFS and OS were 75%, 63%, 87%, and 77%, respectively. Despite VSLI exposure of up to 35 mg, the safety profile of CHMP±R was comparable to that reported for CHOP±R. Grade 3 peripheral neuropathy was reported in 2 (3%) patients; there was no reported Grade 3/4 constipation. CHMP±R was highly active, generally well tolerated, and compared favourably to historical trials with R-CHOP in DLBCL. This enhanced activity probably reflects VCR dose intensification, pharmacokinetic optimization, and enhanced delivery afforded by VSLI. A Phase 3 trial of R-CHMP versus R-CHOP in elderly patients with untreated DLBCL is ongoing.
British Journal of Haematology 06/2013; 162(5). DOI:10.1111/bjh.12446 · 4.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Information on the impact of hormone receptor status subtypes in breast cancer (BC) prognosis is still limited for Hispanics. We aimed to evaluate the association of BC molecular subtypes and other clinical factors with survival in a hospital-based female population of BC cases in Puerto Rico. We analyzed 663 cases of invasive BC diagnosed between 2002 and 2005. Information on HER-2/neu (HER-2) overexpression, estrogen (ER), and progesterone (PR) receptor status and clinical characteristics were retrieved from hospitals cancer registries and record review. Survival probabilities by covariates of interest were described using the Kaplan-Meier estimators. Cox proportional hazards models were employed to assess factors associated with risk of BC death. Overall, 17.3% of BC cases were triple-negative (TN), 61.8% were Luminal-A, 13.3% were Luminal-B, and 7.5% were HER-2 overexpressed. In the multivariate Cox model, among patients with localized stage, women with TN BC had higher risk of death (adjusted hazard ratio [HR]: 2.57, 95% confidence interval [CI]: 1.29-5.12) as compared to those with Luminal-A status, after adjusting for age at diagnosis. In addition, among women with regional/distant stage at diagnosis, those with TN BC (HR: 5.48, 95% CI: 2.63-11.47) and those HER-2+, including HER-2 overexpressed and Luminal-B, (HR: 2.73, 95% CI:1.30-5.75) had a higher mortality. This is the most comprehensive epidemiological study to date on the impact of hormone receptor expression subtypes in BC survival in Puerto Rico. Consistent to results in other populations, the TN subtype and HER-2+ tumors were associated with decreased survival.
Cancer Medicine 06/2013; 2(3):343-50. DOI:10.1002/cam4.78 · 2.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The combination of rituximab and lenalidomide has shown promise for the treatment of mantle-cell lymphoma (MCL) in preclinical studies. We aimed to identify the maximum tolerated dose (MTD) of lenalidomide when combined with rituximab in a phase 1 trial and to assess the efficacy and safety of this combination in a phase 2 trial in patients with relapsed or refractory MCL.
Patients with relapsed or refractory MCL who had received one to four previous lines of treatment were enrolled in this single-arm, open-label, phase 1/2 trial at MD Anderson Cancer Center. In phase 1, to identify the MTD of lenalidomide, four patient cohorts received escalating doses (10, 15, 20, and 25 mg) of daily oral lenalidomide on days 1-21 of each 28-day cycle. 375 mg/m(2) intravenous rituximab was also administered in four weekly doses during cycle 1 only. In phase 2, patients received rituximab plus the MTD of lenalidomide, following the same cycles as for phase 1. Treatment in both phases continued until disease progression, stem-cell transplantation, or severe toxicity. The primary efficacy endpoint was overall response (complete or partial response). The secondary efficacy endpoint was survival. We used the Kaplan-Meier method to estimate response duration, progression-free survival, and overall survival. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00294632.
52 patients were enrolled between Feb 10, 2006 and July 30, 2009, 14 in phase 1 and 44 (including six patients who received the MTD of lenalidomide in the phase 1 portion) in phase 2. The MTD was 20 mg lenalidomide. One patient who was treated with 25 mg lenalidomide developed a grade 4 non-neutropenic infection and died. In the phase 2 portion of the study, grade 3-4 haematological toxicities included neutropenia (29 patients), lymphopenia (16 patients), leucopenia (13 patients), and thrombocytopenia (ten patients). There were only two episodes of febrile neutropenia. Among 44 patients in phase 2, 25 (57%) had an overall response: 16 (36%) had a complete response and nine (20%) had a partial response. The median response duration was 18·9 months (95% CI 17·0 months to not reached [NR]). The median progression-free survival was 11·1 months (95% CI 8·3 to 24·9 months), and the median overall survival was 24·3 months (19·8 months to NR). Five of 14 patients who had received bortezomib treatment before enrolment achieved an overall response.
Oral lenalidomide plus rituximab is well tolerated and effective for patients with relapsed or refractory MCL.
The Lancet Oncology 06/2012; 13(7):716-23. DOI:10.1016/S1470-2045(12)70200-0 · 24.69 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Triple-negative breast cancer (TNBC) demonstrates unique clinicopathological characteristics and survival outcomes. Several studies have documented important disparities in Hispanic women compared to other racial/ethnic groups; nevertheless, data on this entity in a population based Latin country are very limited. Our goal was to assess demographic and clinicopathological characteristics in essentially a pure population of Puerto Rican females with TNBC residing in Puerto Rico, as well as to determine their overall survival and progression-free survival in order to compare with published data.
By searching the electronic medical records data base, 54 patients were identified as TNBC. The median follow-up period was 25 months (range, 2-78). Univariate analysis of pretreatment risk factors was conducted. Results: The median age at diagnosis was 55 years. Of 54 cases, 51 had stage I-III presentation. T1/T2 tumors were found in 88.9% and absence of nodal involvement in 68.5%. Prognostic factors for progression free survival (PFS) that were statistically significant were lymph node involvement (p = 0.02), tumor size > 2 cm (p = 0.037) and stage IV (p = 0.00002). The 5-year overall survival and PFS were 81% and 80%, respectively.
Results are very similar to published data on females from North America and Europe. Differences in clinical outcome and stage at diagnosis in Hispanic women with TNBC are more likely explained by socioeconomic status and adequate access to care, rather than biological/genetic differences. The association of triple-negative breast cancer with poor prognosis deserves re-evaluation given that patients with negative node involvement and no metastasis appear to be highly
Puerto Rico health sciences journal 06/2012; 31(2):45-51. · 0.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Currently the choice of chemotherapy regimen in rectal cancer is made prior to surgery in contrast to colon cancer where it is made postoperatively after the pathological stage has been determined. If we could identify which are the important pretreatment prognostic factors in rectal cancer, we could then target those patients with unfavorable features to investigate potentially more effective preoperative chemotherapy regimens aimed at those with unfavorable features. The present study aimed to determine pre-treatment prognostic factors that are associated with an unfavorable outcome.
A retrospective review of 99 rectal cancer patients operated at the Auxilio Mutuo Hospital, San Juan, Puerto Rico, and the San Pablo Hospital, Bayamón, Puerto Rico was done. Socio-demographic, clinical and treatment data were collected.
Of the 99 cases, 54% were males. The mean age +/- standard deviation was 62.2 +/- 10.4. In age-adjusted Cox model, male gender (HR [95%CI]: 3.32 [1.09-10.13]), mucinous carcinoma (HR [95% CI]: 3.67 [1.25-10.77]), and clinical stages II & III (HR [95%CI]: 8.19 [1.08-62.08]) were predictors of poor prognosis. In the multivariate age-adjusted analysis, a tendency towards a poorer prognosis was observed for male patients (HR: 2.60), carcinoembryonic antigen level > or =5 ng/ml (HR: 2.55), mucinous carcinoma (HR: 2.96), and clinical stages II & III (HR: 4.96), although results were not statistically significant (p > 0.05).
Although current therapeutic results are relatively favorable with preoperative 5-fluorouracil and radiotherapy, future clinical trials should address the management of those cases with adverse pretreatment prognostic factors so that they can be treated with potentially more effective albeit more toxic chemotherapy regimens.
Puerto Rico health sciences journal 06/2012; 31(2):52-8. · 0.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This update will focus on new developments which can impact the understanding and management of patients with DLCL. The latter disorder is mostly derived from B lymphocytes which can be further subdivided into those that originate from the germinal center versus those that arise from non-germinal center areas in the lymph node. The differences between these two types will be discussed. The management of several new entities that relate to DLCL such as 'double hit lymphoma' and so called borderline entities will also be featured. New entities such as breast implant associated anaplastic large cell lymphoma will be described.
[Show abstract][Hide abstract] ABSTRACT: Granulocyte-macrophage colony stimulating factor (GM-CSF) has been associated with multiple immune effects, which could enhance the outcome of chemotherapy. For this reason we decided to explore the combination of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) given every 14 days with pegfilgrastim (Neulasta) and GM-CSF (Leukine). A total of 59 HIV-negative patients with aggressive-histology non-Hodgkin lymphoma were accrued. The median age was 56 years (range 25-87). Lactate dehydrogenase (LDH) was high in 36 patients (61%); performance status was 0-1 in 48 patients; International Prognostic Index (IPI) was 0-1 in 30 and 2-3 in 24 patients; and disease was stage I-II in 46% and III-IV in 56% of patients. Diffuse large B-cell lymphoma was the most common lymphoma type. Response rates were: complete remission (CR) in 51 (86%), partial remission (PR) in five (8%) and failure in three patients (5%). At a median follow-up of 26 months, the overall survival (OS) at 3 years was 76% and the 3-year failure-free survival (FFS) was 73%. No patient relapsed beyond 18 months. Patients with IPI ≥ 3 had a 3-year progression-free survival (PFS) of 54% versus 82% in those with IPI < 3 (p = 0.038). Patients aged < 60 years had a FFS of 77% while those aged ≥ 60 years had a FFS of 69% (p = 0.29). Both the CR rate and the quality of CRs were satisfactory, with only 5/51 (10%) of complete responders having lost their remissions to date. Of interest is that age ≥ 60, an important adverse prognostic factor, appeared to have lost some of its importance, since the difference between those aged < 60 and ≥ 60 years was minimal in our study. The results with R-CHOP-GM-CSF every 14 days are encouraging, and merit a prospective comparative clinical trial against R-CHOP-14 in order to elucidate the contribution of GM-CSF.
[Show abstract][Hide abstract] ABSTRACT: Elevated serum CD44, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) have been linked to poor prognosis in aggressive lymphomas, but their utility in low grade lymphomas remains undefined. We evaluated serum CD44, VCAM-1 and ICAM-1 levels in 100 patients with newly diagnosed indolent NHL. The median pre-treatment values of the markers were as follows: CD44 540 ng/mL (range 156-1201), ICAM-1 311 ng/mL (range 102-1222) and VCAM-1 1165 ng/mL (range 248-4779). On univariate analysis, elevated sCD44, sICAM-1 and sVCAM-1 were significantly associated with worse overall (OS) and progression-free survival (PFS). In a subset analysis of patients with stage IV disease, the effects of sCD44 and sICAM-1 on OS persisted (p<0.05), as did the effect of sCD44 on PFS (p<0.01). In a multivariate analysis that included conventional prognostic factors and the Follicular Lymphoma International Prognostic Index (FLIPI) model, sICAM-1 demonstrated prognostic value for OS and PFS. We conclude that serum CD44, ICAM-1 and VCAM-1 can potentially be prognostic in patients with indolent NHL. Though the FLIPI model remains the gold standard for prognosis, these quantitative serologic markers may be useful as adjunct tools in assessing disease risk.
[Show abstract][Hide abstract] ABSTRACT: During the past decade we have witnessed a number of changes in the field of non-Hodgkin lymphoma (NHL), including new entities added to the classification as well as a better understanding of the biology of diffuse large B-cell lymphoma (DLBCL). An understanding of the epigenetics of NHL is also contributing new agents for the management of this disorder. It has become increasingly clear that DLBCL is a biologically and clinically heterogeneous cell type. Two major categories are now recognized: germinal center B cell and activated B-cell (ABC) types. The former is associated with a good prognosis while the latter is known to have a more adverse outcome. With the use of routine immunohistochemical stains, these two types can be identified. The ABC type is known to be NFK-B dependent. NFK-B is a therapeutic target for bortezomib which is being investigated as treatment for this subtype of DLBCL. Several major changes in the classification will be discussed among which the most important are the recognition of so-called borderline entities. One of the two most common of these is the borderline DLBCL/Burkitt tumor (DLBCL/BL) which has features of both DLBCL and Burkitt's lymphoma. Many of the cases in this DLBCL/BL category contain a translocation of MYC as well as BCL2, so-called "double-hit lymphomas" which have a very aggressive clinical behavior. The second common borderline entity is the mediastinal grey zone NHL (MGZL) which has pathological features intermediate between primary mediastinal B-cell lymphoma and nodular sclerosing Hodgkin lymphoma (NSHL). Overlapping clinical features include young age, male predominance, and localized mediastinal presentation. Anecdotal reports suggest MGZL is relatively resistant to Hodgkin-based chemotherapy. Epigenetic therapy represents a new concept. Histone deacetylase inhibitors (HDACi)and DNA methyltransferase inhibitors constitute a promising new class of antineoplastic agents. They modify the expression of genes related to cancer development. In this review, we discuss the role of HDACi in lymphomagenesis as well as in treatment. To understand the benefits of HDACi in lymphoma treatment, we must appreciate the crucial interplay between BCL6, p53, and STAT3. The STAT3 oncogene is involved in the ABC type of DLBCL, an unfavorable and frequently therapy-refractory lymphoma. STAT3 can be effectively suppressed by several HDACi. We will summarize the results of recent trials with HDACi such as romidepsin, panobinostat and valproic acid that have shown significant preliminary activity in recurrent and refractory lymphomas. Their future role in front-line management remains to be determined.
[Show abstract][Hide abstract] ABSTRACT: Pancreatic cancer is an aggressive, frequently fatal malignancy that strikes 37,000 patients annually in the U.S.A. It is poorly responsive to standard chemotherapies such as gemcitabine. Approximately 5-10% of pancreatic cancer occurs in the setting of a BRCA2 mutation. Breast and ovarian carcinomas that harbor BRCA2 mutations are susceptible to the effects of an emerging class of targeted agents, namely, poly(ADP-ribose) polymerase (PARP) inhibitors. This report describes the case of a patient with a germline BRCA2 mutation and an associated pancreatic cancer treated with iniparib (BSI-201), a PARP inhibitor, who demonstrated a complete pathologic response to this agent. This case highlights the potential benefit for PARP inhibition in BRCA2-related pancreatic cancer.
Anticancer research 04/2011; 31(4):1417-20. · 1.83 Impact Factor