Efficacy and safety of sorafenib-gemcitabine combination therapy in advanced hepatocellular carcinoma: an open-label Phase II feasibility study

Sorafenib is considered a standard of care in advanced hepatocellular carcinoma [HCC]. Its combination with gemcitabine, a pyrimidine analogue with limited friendly hepatic profile may prove beneficial in advanced HCC. The primary objective was to evaluate the efficacy and safety of a sorafenib and gemcitabine combination in patients with advanced HCC. This was a non-randomized, open-label, single-arm, multi-centric Phase II study conducted in Pakistan where 30 treatment-naive patients aged between 26 and 73 years with Child-Pugh score A or B were treated with sorafenib [400 mg oral] twice daily for 16 weeks along with gemcitabine [1000 mg/m[2] intravenous] administered on day 1 and day 8 of a four-week cycle for 16 weeks. Of the 18 patients [60%] who completed all four cycles of treatment, eight patients had stable disease, two had partial response, and eight had progressive disease. There was no complete response. The most common [>/= 10% patients] treatment-emergent adverse events were gemcitabine-related thrombocytopenia [40%] followed by sorafenib-related hand-foot skin reaction and anorexia [33% each]. The efficacy of sorafenib gemcitabine combination therapy is similar to the sorafenib alone treatment. However, frequent dose adjustments due to gemcitabine-related toxicities, delays, and corrective treatments make this combination therapy unsafe in the treatment of advanced HCC.

multicentre phase-II feasibility study evaluating gemcitabine/ vinorelbine / prednisolone combination chemotherapy in relapsed / refractory Hodgkin's lymphoma

To determine the efficacy and toxicity of Gemcitabine, Vinorelbine and Prednisolone [GVP] salvage chemotherapy in relapsed / refractory Hodgkin's Lymphoma [HL]. A phase-II non-randomized single arm study. This study was conducted at Combined Military Hospital and Medical College Lahore, Mayo Hospital, King Edward Medical University, Lahore, Allied Hospital, Punjab Medical College, Faisalabad and Combined Military Hospital, Rawalpindi, from January 2007 to December 2007. Fifty adult patients with relapsed/refractory HL, adequate marrow reserve, hepatorenal and pulmonary functions, with radiological measurable disease and Karnofsky performance status of 0 - 2 non-candidates for stem cell transplantation, were enrolled. Four 28 days cycles of GVP [Gemcitabine 1000 mg/m2, Vinorelbine 30 mg/m2 on day 1 and 8 intravenously with oral Prednisolone 100 mg/day on day 1 - 5] were given. Response evaluation done according to Cotswolds meeting recommendations and toxicity was evaluated with NCI-CTC [National Cancer Institute - Common Terminology Criteria for adverse events v 3.0]. Forty patients completing 4 cycles of GVP, 14 refractory/early relapse and 26 late relapsed [one year postprimary treatment with ABVD] were available for evaluation. The overall response [CRu+PR] rate was 77.5% with better response 85% in late relapsed patients. Haematological toxicity was most common and seen in 70% of cases. GVP is well-tolerated regimen with high response rate and needs to be tested in late relapsed H

Neutrrophil toxicity and primary prophylaxis in diffuse large B cell lymphoma treated with R-chop

To identify the risk of neutrophil toxicity in patients of advanced stage Diffuse Large B Cell Lymphoma [DLBCL] patients with low to intermediate-risk International prognostic index [IPI] treated with three weekly R-CHOP therapy. Quasi-experimental study. Combined Military Hospital Rawalpindi on 50 patients of advanced stage DLBCL from 1st Jan 2009 to 31st Dec 2009. Patients were observed for occurrence of significant neutrophil toxicity defined as grade 4 neutropenia between day 7 and 10 post therapy, febrile neutropenia and grade 2 or more neutrophil toxicity persisting on day 1 of next cycle. NCI Common Toxicity Criteria version 3.0 was used for grading toxicity. Patients with WHO Performance status scale 4, on immunosuppressive drugs, abnormal hepatic or renal functions and inadequate hematological values were excluded. Fourteen [28%] patients had poor performance status [WHO 2] and amongst them grade 4 neutrophil toxicity was seen in 8[57%] and 3 got complicated with febrile neutropenia. In the remaining 36 [72%] patients with good performance status [WHO 0 or 1] only 2[5.5%] developed grade 4 toxicity none getting complicated with febrile neutropenia. Frequency of neutrophil toxicity was 20% in Non Hodgkin's Diffuse Large B Cell Lymphomas [Low and Intermediate IPI] patients treated with 3 weekly R-CHOP. Patients with WHO performance status scale 2 are high-risk for developing significant neutrophil toxicity and therefore require primary neutropenia prophylaxis

Falciparum malaria; comparison of response to treatment between quinine and artemether

Quinine and quinidines remain the drugs of choice for chloroquine resistant Plasmodium falciparum malaria. In 1972, Chinese scientists discovered the antimalarial properties of a group of compounds from the qinghao plant [Artemisia annua] which have activity against all malaria causing parasites including multi-drug resistant strains of Plasmodium falciparum. To compare response to treatment between quinine and artemether in Plasmodium falciparum malaria. Quasi-experimental study. Department of Medicine Pakistan Air Force Hospital Lahore. 1st Jun 2008 to 1st Dec 2009. 80 consecutive adult patients with positive MP slide for Plasmodium falciparum malaria. Patients were randomly divided into two groups for treatment either with quinine or artemether. Out of total 80 patients, 40 were given quinine and 40 were given artemether. Out of 40, 16 patients responded to quinine while 24 did not respond. The responders were 34.8% in case of quinine while 70.6% patients did not respond. Out of 40 patients treated with artemether, 30 responded while 10 did not. The responders were 65.2%while non responders were 29.4%. On calculating the P-value from the chi-square it was found that difference in terms of response to the two treatment regimens was statistically significant.[P=.0022]. The frequency of response in case of quinine was 34.8% while it was 65.2% in case of artemether. So based upon statistically significant difference [P=.0022] it is concluded that Artemether is a satisfactory alternative to Quinine for the treatment of falciparum malaria in adults

Presenting phases of chronic myeloid leukaemia

To determine the frequency of three phases of chronic myeloid leukaemia at first presentation. Department of Oncology, Combined Military Hospital [CMH], Rawalpindi, from June 2006 to December 2007. Forty-five patients of either gender with Chronic Myeloid Leukaemia [CML] at their first presentation in outpatient department were included in the study by consecutive sampling technique. All patients were diagnosed on blood complete picture and bone marrow examination including aspiration, trephine and cytogenetics at Armed Forces Institute of Pathology [AFIP]. Each phase was defined on the basis of World Health Organization [WHO] criteria. Out of 45, there were 31 [68.9%] male and 14 [31.1%] female patients. The mean age of presentation was 37.9 years. The pattern of presentation revealed 35 [77.8%] in Chronic Phase [CP], 7 [15.5%] in Accelerated Phase [AP] and 3 [6.7%] in Blast Crisis [BC]. Philadelphia chromosome was detected in 39 [86.7%] cases on culture method. Splenomegaly was observed in 37 [82.2%] patients. The mean total leukocyte count, platelet count, haemoglobin and marrow blast were 214.3x10[9]/L, 551.4x10[9]/L, 9.94 g/dl and 9.3% respectively. CML presented at a younger age in the chronic phase

Frequency of bone marrow involvement in Hodgkin's lymphoma on first presentation

To determine the frequency of bone marrow involvement in patients of Hodgkin's lymphoma on first presentation at oncology department. Case series. The Oncology Department, Combined Military Hospital, Rawalpindi, from April 2006 to February 2007. Thirty five patients of Hodgkin's lymphoma diagnosed on lymph node biopsy presenting for the first time at Oncology Department, Combined Military Hospital, Rawalpindi were included. They were admitted in the ward and evaluated with history, physical examination and staging investigations. Bone marrow trephine biopsy was performed in all patients. Descriptive statistics were used to analyze data. On clinical and radiological evaluation, 8 patients [22.9%] had clinical stage [CS], 12 [34.3%] had CS II, 9 [25.7%] had CS III and 6 [17.1%] had CS IV. The microscopic appearance in bone marrow trephine examination showed lymphoma infiltrates in 6 [17.14%] patients and chronic disorder in 29 [82.85%] patients. Among patients with bone marrow infiltration, one had CS II disease, three had CS III disease and two had CS IV disease. One patient had bone marrow infiltration as the only manifestation of disease. Bone marrow involvement was seen in patients with Hodgkin's lymphoma clinical stage II or higher

Microalbuminuria: association with ischaemic heart heart disease in non-diabetics

In view of the high morbidity and mortality associated with ischemic heart disease [IHD], the estimation of individual cardiovascular risk over and above the assessment of classic risk factors, such as age, hypercholesterolemia and hypertension, is an important prerequisite for focusing preventive measures and therapeutic measures. Microalbuminuria [MA] as a marker of IHD in nondiabetics is currently under international debate. The present descriptive study undertaken at Combined Military Hospital, Lahore was aimed to determine the frequency of MA in nondiabetic IHD patients. One hundred consecutive non diabetic patients with IHD [73 males, 27 females]. Patients showing clinical albumiuria and with other causes of proteinuria were excluded. Urinary albumin in first morning sample was estimated by immunoturbidimetry method. Albumin to creatinine ratio [ACR] was calculated as mg/g. The frequency of MA [ACR > 30 mg/g] was 37% in patients. Frequency was highest in older age bracket for both genders. The mean ACR was 131.8 +/- 66.2 mg/g. Significant difference was observed in mean MA level among different age groups. MA is common in nondiabetics patients with IHD. The mean level of MA was higher in older patients

Clinical features in accelerated phase of chronic myeloid leukemia

To identify the clinical indicators of accelerated phase in chronic myeloid leukemia [CML] diagnosed on hematological findings. Design: An observational and prospective study. Place and Duration of Study: The study was conducted at Oncology department of Combined Military Hospital, Rawalpindi and Armed Forces Institute of Pathology from April 1998 to April 1999. Subjects and The study on 51 patients of Philadelphia positive CIVIL in chronic phase and on hydroxyurea therapy were carried out. Clinical features and hematological parameters in the peripheral blood examination were recorded and statistical analysis carried out to document reliable clinical indicators of accelerated phase of CIVIL in reference to those reported in the literature. Clinically, presence of unexplained fever, re-enlargement of spleen after successful regression with hydroxyurea therapy, and bleeding diathesis were found to be statistically significant pointers of progression into accelerated phase of CML. In the hematological features, with the exception of peripheral basophilia, the findings in the peripheral blood were consistent with those reported in the literature. It is concluded that the occurrences of the forementioned clinical features in the follow-up of chronic myeloid leukemia patients herald the accelerated phase of the disease