Current Issue : January - March Volume : 2017 Issue Number : 1 Articles : 5 Articles
Background: To better evaluate and improve the efficacy of dendritic cell (DC)-based cancer immunotherapy,\nwe conducted a clinical study of patients with advanced colorectal cancer using carcinoembryonic antigen\n(CEA)-pulsed DCs mixed with tetanus toxoid and subsequent interleukin-2 treatment. The tetanus toxoid in\nthe vaccine preparation serves as an adjuvant and provides a non-tumor specific immune response to enhance vaccine\nefficacy. The aims of this study were to (1) evaluate the toxicity of this treatment, (2) observe the clinical responses of\nvaccinated patients, and (3) investigate the immune responses of patients against CEA before and after treatment.\nMethods: Twelve patients were recruited and treated in this phase I clinical study. These patients all had metastatic\ncolorectal cancer and failed standard chemotherapy. We first subcutaneously immunized patients with metastatic\ncolorectal cancer with 1 Ã?â?? 106 CEA-pulsed DCs mixed with tetanus toxoid as an adjuvant. Patients received 3 successive\ninjections with 1 Ã?â?? 106 CEA-pulsed DCs alone. Low-dose interleukin-2 was administered subcutaneously following the\nfinal DC vaccination to boost the growth of T cells. Patients were evaluated for adverse event and clinical\nstatus. Blood samples collected before, during, and after treatment were analyzed for T cell proliferation\nresponses against CEA.\nResults: No severe treatment-related side effects or toxicity was observed in patients who received the regular 4 DC\nvaccine injections. Two patients had stable disease and 10 patients showed disease progression. A statistically\nsignificant increase in proliferation against CEA by T cells collected after vaccination was observed in 2 of 9 patients.\nConclusions: The results of this study indicate that it is feasible and safe to treat colorectal cancer patients using this\nprotocol. An increase in the anti-CEA immune response and a clinical benefit was observed in a small fraction of\npatients. This treatment protocol should be further evaluated in additional colorectal cancer patients with modifications\nto enhance T cell responses....
Background: This paper describes about a study protocol of phase I/II multicenter prospective clinical trial\nevaluating the feasibility and efficacy of the hybrid of intracavitary and interstitial brachytherapy (HBT) for locally\nadvanced uterine cervical cancer patients.\nMethods and design: Patients with histologically confirmed FIGO stage IB2, IIA2, IIB, and IIIB uterine cervical\ncarcinoma width of which is larger than 5 cm assessed by MRI will be entered to this clinical trial. Protocol therapy\nis 30-30.6 Gy in 15-17 fractions of whole pelvic radiotherapy concurrent with weekly CDDP (40 mg/m2), followed by\n24 Gy in 4 fractions of HBT and central shield EBRT up to 50-50.4 Gy in 25-28 fractions. Tumor width is assessed\nagain within one week before the first HBT and if the tumor width is larger than 4 cm, patients proceed to the\nsecondary registration. In phase I section, feasibility of this will be investigated. If less than 10 % out of 20 patients\nexperienced greater than grade 3 acute non-hematologic adverse effects, the study proceeds to phase II part. In\nphase II part a total of 55 patients will be accrued and the efficacy of the HBT will be investigated comparing with\nhistorical control data. If the lower margin of 90 % confidence interval of the 2-year pelvic progression-free survival\nof the HBT trial is higher than 64 %, the HBT is considered to be more effective than conventional ICBT.\nDiscussion: The aim of this study is to demonstrate the feasibility and efficacy of the HBT for locally advanced\ncervical cancer. This trial will clarify the indication, feasibility, and efficacy of this new technique....
Background: Chronic lymphocytic leukaemia (CLL) is the most common adult leukaemia. Combination\nimmunochemotherapy such as fludarabine, cyclophosphamide and rituximab is the standard first line therapy\nin fit patients, but there is limited evidence regarding the optimal treatment of patients after relapse. Ofatumumab as\nmonotherapy has been proven to be effective in the treatment of relapsed, refractory CLL, and as it is not myelotoxic,\nit is an ideal drug to combine with chemotherapy. However, the optimal dose of ofatumumab in this setting is not\nknown. The Chemotherapy plus Ofatumumab at Standard or Mega dose in relapsed CLL (COSMIC) trial will assess the\nefficacy and safety of standard and high (mega) doses of ofatumumab combined with bendamustine or a combination\nof fludarabine and cyclophosphamide to determine which, if either, schedule should progress to a phase III trial.\nMethods/design: COSMIC is a phase II, multi-centre, randomised, open, parallel group trial for patients with relapsed\nCLL who are not refractory to fludarabine-based chemotherapy. Participants will be randomised to receive either\nstandard dose or mega dose ofatumumab. Both doses will be given in combination with either bendamustine or\nfludarabine and cyclophosphamide chemotherapy backbone. The primary objective is to assess the proportion of\nparticipants achieving a complete remission following therapy with the two treatment arms (mega versus\nstandard), as assessed at 3 months post treatment. The treatment groups will be assessed independently to determine\nwhether the level of response is acceptable in relation to pre-specified criteria. If both treatment groups show an\nacceptable level of response, selection criteria will be used to determine which to take forward to a confirmatory\nphase III trial. A key secondary objective is to assess the dynamics of minimal residual disease (MRD) levels in\nrelapsed disease. Eighty-two participants are planned to be recruited from 18 research centres in the UK.\nDiscussion: Currently there is limited evidence regarding the optimal treatment of patients with relapsed or refractory\nCLL, and so suitable therapies are urgently needed. The COSMIC trial will identify whether ofatumumab given\nin combination with chemotherapy is safe and effective in this population, and will identify the optimal doses\nfor further investigation....
Background: Colorectal cancer (CRC) is the fourth most frequently diagnosed cancer and the second leading cause\nof neoplasm-related death in the United States. Several studies analyzed the efficacy of bevacizumab combined\nwith different chemotherapy regimens consisting on drugs such as 5-FU, capecitabine, irinotecan and oxaliplatin.\nThis systematic review aims to evaluate the effectiveness and safety of chemotherapy plus bevacizumab versus\nchemotherapy alone in patients with previously untreated advanced or metastatic colorectal cancer (mCRC).\nMethods: Several databases were searched, including MEDLINE, EMBASE, LILACS, and CENTRAL. The primary\nendpoints were overall survival and progression-free survival. Data extracted from the studies were combined by\nusing hazard ratio (HR) or risk ratio (RR) with their corresponding 95 % confidence intervals (95 % CI).\nResults: The final analysis included 9 trials comprising 3,914 patients. Patients who received the combined\ntreatment (chemotherapy + bevacizumab) had higher response rates (RR = 0.89; 95 % CI: 0.82 to 0.96; p = 0.003)\nwith heterogeneity, higher progression-free survival (HR = 0.69; 95 % CI: 0.63 to 0.75; p < 0.00001) and also higher\noverall survival rates (HR = 0.87; 95 % CI: 0.80 to 0.95; p = 0.002) with moderate heterogeneity. Regarding adverse\nevents and severe toxicities (grade � 3), the group receiving the combined therapy had higher rates of hypertension\n(RR = 3.56 95 % CI: 2.58 to 4.92; p < 0.00001), proteinuria (RR = 1.89; 95 % CI: 1.26 to 2.84; p = 0.002), gastrointestinal\nperforation (RR = 3.63; 95 % CI: 1.31 to 10.09; p = 0.01), any thromboembolic events (RR = 1.44; 95 % CI: 1.20 to\n1.73; p = 0.0001), and bleeding (RR = 1.81; 95 % CI: 1.22 to 2.67; p = 0.003).\nConclusion: The combination of chemotherapy with bevacizumab increased the response rate, progression-free\nsurvival and overall survival of patients with mCRC without prior chemotherapy. The results of progression-free\nsurvival (PFS) and overall survival (OS) were comparatively higher in those subgroups of patients receiving bolus\n5-FU or capecitabine-based chemotherapy plus bevacizumab, when compared to patients treated with infusional\n%-FU plus bevacizumab (no difference in PFS and OS). Regarding the type of cytotoxic scheme, regimens containing\nirinotecan and fluoropyrimidine monotherapy showed superior efficacy results when combined to bevacizumab....
Background: To report toxicity and early clinical outcomes of hypofractionated simultaneous integrated boost (SIB)\napproach with Volumetric Modulated Arc Therapy (VMAT) as adjuvant treatment after breast-conserving surgery.\nMethods: Patients presenting early-stage breast cancer were enrolled in a phase II trial. Eligibility criteria: age > 18 years\nold, invasive cancer or ductal carcinoma in situ (DCIS), Stage I-II (T < 3 cm and N ââ?°Â¤ 3), breast-conserving surgery without\noncoplastic reconstruction. Any systemic therapy was allowed in neoadjuvant or adjuvant setting. All patients\nunderwent VMAT-SIB technique to irradiate the whole breast and the tumor bed. Doses to whole breast and surgical\nbed were 40.5 Gy and 48 Gy, respectively, delivered in 15 fractions over 3 weeks. Acute and late skin toxicities were\nrecorded. Cosmetic outcome was assessed as excellent/good or fair/poor.\nResults: The present study focused on results of a cohort of 144 patients with a minimum follow-up of 24 months\n(median 37, range 24ââ?¬â??55 months). Median age was 62 years old (range 30ââ?¬â??88). All patients had an invasive\ncarcinoma (no patients with DCIS were present in this subset). At one year, the highest reported skin toxicity was\nG1, in 14 % of the patients; this data dropped to 4 % at the last follow-up, after more than 2 years. Breast pain was\nrecorded in 21.6 % of the patients 6 months after treatment, while it was present in 3.5 % of the patients at the\nlast follow-up, showing a significant improvement with time. Correlation between liponecrosis and boost target\nvolume was found not significant. Breast pain was correlated with breast volume. No pulmonary or cardiological\ntoxicities were recorded. After an early evaluation of clinical outcomes, only one case presented disease relapse, as\nliver metastases.\nConclusions: The 3-week VMAT-SIB course as adjuvant treatment after breast-conserving surgery showed to be\nwell tolerated and was associated with optimal local control. Long-term follow-up data are needed to assess late\ntoxicity and clinical outcomes....
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