A phase II study of lipoplatin (liposomal cisplatin)/vinorelbine combination in HER-2/neu-negative metastatic breast cancer.

UNLABELLED: We assessed the efficacy and safety of a liposomal cisplatin (lipoplatin) and vinorelbine combination in metastatic breast cancer (MBC). Thirty-five patients were treated. The objective response rate was 53.1% and the median survival time was 22 months. Grade 3/4 neutropenia was observed in 44% of cycles, and febrile neutropenia was seen in 4 patients (11.4%). No grade 3/4 nephrotoxicity or neuropathy was noted. This combination is effective and well tolerated in patients with MBC and it warrants investigation as first-line treatment. BACKGROUND: Liposomal cisplatin (lipoplatin) has a mechanism of action similar to that of cisplatin, with reduced toxicities and enhanced or similar efficacy. We wanted to assess the efficacy and safety of a lipoplatin/vinorelbine combination in a phase II clinical trial in metastatic breast cancer (MBC). METHODS: Thirty-five patients with HER-2/neu-negative (HER-2/neu(-)) MBC were enrolled. Lipoplatin 120 mg/m(2) (days 1, 8, and 15) and vinorelbine 30 mg/m(2) (days 1 and 8) were administered in a 21-day cycle. RESULTS: Thirty-five patients were included in the intent-to-treat (ITT) analysis; 32 patients were evaluable for response. The objective response rate was 53.1%. Complete response (CR) was achieved in 3 patients (9.4%), partial response (PR) was seen in 14 patients (43.8%), stable disease (SD) was obtained in 12 patients (37.5%), and progressive disease (PD) was seen in 3 patients (9.4%). Median time to disease progression was 8 months (range 6-10 months). After a median follow-up of 15.5 months, 18 patients were still alive; the median survival time was 22 months (95% confidence interval [CI], 14-30). A total of 174 cycles were administered. Neutropenia was the most frequent hematologic toxicity, with grade 3/4 neutropenia observed in 44% of cycles. Febrile neutropenia was observed in 4 patients (11.4%). No grade 3/4 nephrotoxicity or neuropathy was noted. Grade 1/2 nephrotoxicity occurred in 8 patients (22.9%) and grade 3 vomiting was seen in 3 patients (8.6%). CONCLUSIONS: The results of this trial reveal that vinorelbine/lipoplatin is effective in treating patients with MBC. This regimen is well tolerated with no grade 3/4 nephrotoxicity or neuropathy. The investigation of this regimen as first-line treatment in MBC is warranted.

Treatment of metastatic breast cancer: state-of-the-art, subtypes and perspectives.

Current treatment of metastatic breast cancer (MBC) aims at achieving meaningful clinical responses, improved quality of life, long-term remissions, prolonged survival, and dares to hope for a cure in a small percentage of cases. This article will discuss both consensus and controversies in the management of MBC in the context of the new evolving breast cancer molecular classification. Hormonal therapy remains the mainstay of management of MBC Luminal A and B. Data is emerging on management of ErbB2-positive HR-positive MBC by combining hormonal manipulation and targeted anti-ErbB2 therapy and has recently received regulatory approval in Europe and USA. The optimal use and duration of single agent or combination chemotherapy is discussed. Data and controversies surrounding the use of newer agents such as nab-paclitaxel, ixabepilone, eribulin, and PARP inhibitors as well as trastuzumab is reviewed. Better understanding of pathophysiology has paved the way for the introduction of newer anti-ErbB2 agents such as lapatinib, pertuzumab, T-DM1 and neratinib. Controversies regarding bevacizumab and anti-angiogenesis are discussed. Bisphosphonates have significantly reduced skeletal related events and made significant improvements in the quality of life of patients with MBC. Newer anti-RANK Ligand antibodies show promising results. Significant advances in the understanding of molecular biology of breast cancer have been made and should lead to an improvement in the outcome of MBC. More possibilities of cure can become an attainable goal in the near future.

Is VEGF a predictive biomarker to anti-angiogenic therapy?

Tumor growth and metastasis are dependent on angiogenesis. Inhibiting angiogenesis has therapeutic potentials for treating cancer. Researchers have identified many of the pathways involved in angiogenesis and proposed selective targeted strategies. A high probability of benefit is desirable to justify the choice of anti-angiogenic therapy from an ever-expanding list of expensive new anticancer agents. However, biomarkers of response to anti-angiogenic agents are inconclusive for predicting benefit from these drugs. This paper reviews the most important biomarker of angiogenesis, namely VEGF, in relation to its expression in cancer and the treatment of these cancers through targeting VEGF and its pathways.

Metastasis of colorectal carcinoma to the testes: clinical presentation and possible pathways.

Distant metastasis from colorectal carcinoma most often occurs in the liver and lungs. Metastasis to bones, adrenals, lymph nodes, brain, and skin has also been reported. Metastatic colorectal carcinoma to the testes is very uncommon. Even more uncommon is testicular metastasis from rectal carcinoma. Researchers throughout the last few decades have not acquired a clear understanding of the lymphatic pathways involved in reported cases of testicular metastasis from primary colorectal carcinoma. These cases may present with testicular complaints after or even before the diagnosis of colorectal cancer; this is why it is crucial to differentiate between primary testicular tumor and a secondary one from a colorectal primary. We searched the English medical literature using the MEDLINE/PUBMED database from 1950 through January 2010. Our search yielded 33 cases of testicular metastasis from rectal or colonic carcinoma. These cases are reviewed and summarized. This paper reviews the literature for all cases of testicular metastasis from colonic and rectal adenocarcinomas shedding light on the possible pathways of metastasis. We recommend that physicians be aware of the risk of metastasis from the colorectal region to the testis in their evaluation of patients with testicular symptoms in the setting of colorectal carcinoma.

Ratio between positive lymph nodes and total excised axillary lymph nodes as an independent prognostic factor for overall survival in patients with nonmetastatic lymph node-positive breast cancer.

BACKGROUND: The status of the axillary lymph nodes in nonmetastatic lymph node-positive breast cancer (BC) patients remains the single most important determinant of overall survival (OS). Although the absolute number of nodes involved with cancer is important for prognosis, the role of the total number of excised nodes has received less emphasis. Thus, several studies have focused on the utility of the axillary lymph node ratio (ALNR) as an independent prognostic indicator of OS. However, most studies suffered from shortcomings, such as including patients who received neoadjuvant therapy or failing to consider the use of adjuvant therapy and tumor receptor status in their analysis. METHODS: We conducted a single-center retrospective review of 669 patients with nonmetastatic lymph nodepositive BC. Data collected included patient demographics; breast cancer risk factors; tumor size, histopathological, receptor, and lymph node status; and treatment modalities used. Patients were subdivided into four groups according to ALNR value (<0.25, 0.25-0.49, 0.50-0.74, 0.75-1.00). Study parameters were compared at the univariate and multivariate levels for their effect on OS. RESULTS: On univariate analysis, both the absolute number of positive lymph nodes and the ALNR were significant predictors of OS. On multivariate analysis, only the ALNR remained an independent predictor of OS, with a 2.5-fold increased risk of dying at an ALNR of ⩾0.25. CONCLUSIONS: Our study demonstrates that ALNR is a stronger factor in predicting OS than the absolute number of positive axillary lymph nodes.

Ratio between positive lymph nodes and total excised axillary lymph nodes as an independent prognostic factor for overall survival in patients with nonmetastatic lymph node-positive breast cancer.

BACKGROUND.: The status of the axillary lymph nodes in nonmetastatic lymph node-positive breast cancer (BC) patients remains the single most important determinant of overall survival (OS). Although the absolute number of nodes involved with cancer is important for prognosis, the role of the total number of excised nodes has received less emphasis. Thus, several studies have focused on the utility of the axillary lymph node ratio (ALNR) as an independent prognostic indicator of OS. However, most studies suffered from shortcomings, such as including patients who received neoadjuvant therapy or failing to consider the use of adjuvant therapy and tumor receptor status in their analysis. METHODS.: We conducted a single-center retrospective review of 669 patients with nonmetastatic lymph nodepositive BC. Data collected included patient demographics; breast cancer risk factors; tumor size, histopathological, receptor, and lymph node status; and treatment modalities used. Patients were subdivided into four groups according to ALNR value (<.25, .25-.49, .50-.74, .75-1.00). Study parameters were compared at the univariate and multivariate levels for their effect on OS. RESULTS.: On univariate analysis, both the absolute number of positive lymph nodes and the ALNR were significant predictors of OS. On multivariate analysis, only the ALNR remained an independent predictor of OS, with a 2.5-fold increased risk of dying at an ALNR of ≥.25. CONCLUSIONS.: Our study demonstrates that ALNR is a stronger factor in predicting OS than the absolute number of positive axillary lymph nodes.

Ratio between positive lymph nodes and total excised axillary lymph nodes as an independent prognostic factor for overall survival in patients with nonmetastatic lymph node-positive breast cancer.

BACKGROUND: The status of the axillary lymph nodes in nonmetastatic lymph node-positive breast cancer (BC) patients remains the single most important determinant of overall survival (OS). Although the absolute number of nodes involved with cancer is important for prognosis, the role of the total number of excised nodes has received less emphasis. Thus, several studies have focused on the utility of the axillary lymph node ratio (ALNR) as an independent prognostic indicator of OS. However, most studies suffered from shortcomings, such as including patients who received neoadjuvant therapy or failing to consider the use of adjuvant therapy and tumor receptor status in their analysis. METHODS: We conducted a single-center retrospective review of 669 patients with nonmetastatic lymph node-positive BC. Data collected included patient demographics; breast cancer risk factors; tumor size, histopathological, receptor, and lymph node status; and treatment modalities used. Patients were subdivided into four groups according to ALNR value (< .25, .25-.49, .50-.74, .75-1.00). Study parameters were compared at the univariate and multivariate levels for their effect on OS. RESULTS: On univariate analysis, both the absolute number of positive lymph nodes and the ALNR were significant predictors of OS. On multivariate analysis, only the ALNR remained an independent predictor of OS, with a 2.5-fold increased risk of dying at an ALNR of >or= .25. CONCLUSIONS: Our study demonstrates that ALNR is a stronger factor in predicting OS than the absolute number of positive axillary lymph nodes.

Hypoxia-inducible factor in cancer angiogenesis: structure, regulation and clinical perspectives.

Tumor hypoxia is a common feature of many cancers. A master regulator of hypoxic response is the transcription factor hypoxia-inducible factor-1 (HIF-1). It functions as a master regulator of oxygen and undergoes conformational changes in response to varying oxygen concentrations. In this paper, we review what has been described about HIF-1: its structure, its regulation and target genes, its role in cancer, and its implication for cancer therapy.

Long-term outcome of adult acute lymphoblastic leukemia in Lebanon: a single institution experience from the American University of Beirut.

BACKGROUND AND OBJECTIVES: The most important studies about outcome of acute leukemia come from developed countries, whereas most of the patients with this disease are in developing countries. We report predictive and prognostic factors in patients with acute lymphoblastic leukemia (ALL) in a tertiary care center in a developing country. PATIENTS AND METHODS: We retrospectively reviewed the records of adult patients with acute leukemia who were referred to the American University of Beirut Medical Center between 1996 and early 2006. RESULTS: Of 105 patients, 36 (34%) patients were diagnosed with ALL, and included 19 (53%) males and 17 (47%) females with a median age of 34 years (range, 14-79 years). Induction chemotherapy with curative intent was administered to 34 (94%) patients. Twenty-seven patients received intrathecal chemotherapy as prophylaxis (n=24) or as treatment for CNS disease (n=3). Twenty-eight patients (82%) achieved complete remission (CR) after induction chemotherapy. The median overall survival (OS) time was 22 months and the five-year OS for ALL patients was 38%. The median disease-free survival (DFS) time was 12 months, while the five-year DFS was 38%. Multivariate analysis showed that age <40 years, WBC <30 X 109/L, achievement of CR after first induction, and CNS prophylaxis were predictive factors for OS and DFS. CONCLUSION: Despite limitations and the relatively low socioeconomic status of the Lebanese population, OS (38%) and DFS (38%) are quite similar to international data. Trends toward a higher CR and DFS in adults are due to intensified consolidation chemotherapy, the use of stem cell transplantation, and improvements in supportive care.

Effect of mucin production on survival in colorectal cancer: a case-control study.

AIM: To investigate the impact of mucin production on prognosis in colorectal cancer, in terms of overall survival (OS) and time to disease progression (TTP) in patients with mucinous compared to those with non-mucinous colorectal cancer (NMCRC), matched for age, gender, and tumor stage. METHODS: Thirty five patients with mucinous colorectal cancer (MCRC) were matched for age, gender, and tumor stage with 35 controls having NMCRC. OS and TTP were compared among 4 groups divided according to mucin content: group A (50%-75% mucin), group B (75%-100% mucin), group C or controls (<50% mucin). Group D consisted of all patients with tumors having <75% mucin (controls and groups A together). RESULTS: Median survival in MCRC and NMCRC groups was 46.2 and 112.9 mo, respectively (P=0.26). OS in groups A and B was 70.1 and 32.8 mo (P=0.46), and in groups B and D was 32.8 and 70.1 mo, respectively (P=0.143). TTP in MCRC and NMCRC was 50.17 and 44.77 mo, respectively (P=0.795). TTP in groups A, B, and D was 70.1, 24.8, and 65.5 mo, respectively. Twenty-eight percent of patients with MCRC had poorly differentiated adenocarcinoma versus 8.6% in NMCRC patients (P=0.028). CONCLUSION: MCRC is associated with a non-significant decrease in median survival and TTP, particularly when mucin content is >75% of tumor volume. However, it tends to be more poorly differentiated. A larger study matching for stage and grade is needed.

Non-Hodgkin's lymphoma in a woman with adult-onset Still's disease: a case report.

INTRODUCTION: Adult onset Still's disease is a chronic multisystemic inflammatory disorder characterized by high spiking fever, polyarthralgia and rash. Lymphadenopathy is a prominent feature of adult onset Still's disease and is seen in about 65% of patients. Searching the medical literature using the MEDLINE database from January 1966 through November 2007 we could only find two reported cases of adult onset Still's disease that had progressed to lymphoma. CASE PRESENTATION: We describe a woman who was diagnosed with adult onset Still's disease and developed lymphoma 10 months after the onset of her symptoms. She initially presented with fever and arthritis of the knees, ankles and shoulders, along with a nonpruritic skin rash, myalgia and weight loss. On physical examination she was found to have several enlarged anterior cervical lymph nodes and left posterior auricular lymph nodes all of which were non-tender, immobile and rubbery. Excisional biopsy of the cervical lymph nodes was negative for malignancy. Bone marrow biopsy was also negative for malignancy. She was treated with prednisone. She remained in good health until she presented 10 months later with low back pain, dyspnea and weight loss. Work up revealed malignant lymphoma. She was treated with chemotherapy and was doing well until she presented with abdominal pain. Work up revealed a cirrhotic liver and ascites. She then passed away from hepatorenal syndrome 13 years after the diagnosis of lymphoma. To our knowledge, this is the third reported case of such an occurrence. CONCLUSION: Although the association between adult onset Still's disease and lymphoma has been rarely reported, careful screening for this malignancy in patients suspected to have adult onset Still's disease is warranted.

Acute myeloid leukemia with T-cell receptor gamma gene rearrangement occurring in a patient with chronic lymphocytic leukemia: a case report.

The association of chronic lymphocytic leukemia (CLL) and acute leukemia, either lymphoid or myeloid is a rare event. Our review of the medical literature revealed only 6 cases of CLL transformation to acute myeloid leukemia (AML) (M0, M1 and M2) with no other associated malignancy. We report a similar case but with occurrence of AML-M4 associated with normal cytogenetic analysis and molecular testing but with positive T-cell receptor gamma gene rearrangement rather than the usual Vbeta rearrangement.