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Median Progression-free Survival (median + progression-free_survival)
Selected AbstractsLenalidomide and dexamethasone for the treatment of refractory/relapsed multiple myeloma: dosing of lenalidomide according to renal function and effect on renal impairmentEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 1 2010Meletios A. Dimopoulos Abstract Objectives:, Lenalidomide and dexamethasone (LenDex) is an active regimen for relapsed/refractory multiple myeloma (MM). However, there is limited data for the effect of LenDex on renal impairment (RI) and on renal reversibility. Patients & Methods:, Fifty consecutive patients with relapsed/refractory MM received LenDex in 28-d cycles. Median lines of previous therapies were 2 (range: 1,6). Lenalidomide was administered on days 1,21 according to creatinine clearance (CrCl), while dexamethasone was given at a dose of 40 mg on days 1,4 and 15,18 for the first four cycles and only on days 1,4 thereafter. Results:, Twelve patients (24%) had RI at baseline, defined as CrCl < 50 mL/min. Most patients were pretreated with either thalidomide or bortezomib and > 50% of them were refractory to both drugs. At least partial response was documented in 60.5% and 58% of patients with and without RI. Median progression-free survival (PFS) and overall survival (OS) for all patients was 9 and 16 months, respectively. RI was not associated with an inferior PFS or OS. There were no differences in the incidence of adverse events among patients with and without RI. Three of 12 patients with RI (25%) achieved complete renal response and two (16%) achieved minor renal response with LenDex. Conclusions:, We conclude that LenDex is an active treatment even in heavily pretreated MM. With dosing of lenalidomide according to renal function, LenDex can be administered to patients with RI (who may not have other treatment options) without excessive toxicity. Furthermore, LenDex may improve the renal function in approximately 40% of patients with RI. [source] Centrally necrotizing carcinoma of the breast: clinicopathological analysis of 33 cases indicating its basal-like phenotype and poor prognosisHISTOPATHOLOGY, Issue 2 2010Lin Yu Yu L, Yang W, Cai X, Shi D, Fan Y & Lu H (2010) Histopathology,57, 193,201 Centrally necrotizing carcinoma of the breast: clinicopathological analysis of 33 cases indicating its basal-like phenotype and poor prognosis Aims:, To investigate the clinicopathological features and immunophenotype of centrally necrotizing carcinoma (CNC) of the breast to ascertain its relationship to basal-like phenotype and its prognosis. Methods and results:, The clinical and pathological characteristics of 33 CNCs were reviewed. Immunohis-tochemical study of oestrogen receptor, progesterone receptor, HER2, cytokeratin (CK) 8/18, high-molecular-weight CK (34,E12), CK5/6, CK14, CK17, smooth muscle antigen, p63, vimentin and epidermal growth factor receptor was performed. The striking feature of CNC was a central, necrotic or acellular zone surrounded by a ring-like area of viable tumour cells. The central zone showed three morphological types: predominance of coagulative necrosis (21 cases), predominance of fibrosis and scar tissue (nine cases) and infarction (three cases). Tumour cells displayed invasive ductal carcinoma of high grade. The expression rate of basal-like markers was higher than that of myoepithelial markers (87.9% versus 46.2%). Basal-like subtype was shown by 63.6% of cases. The expression rate of CK5/6 (90.5%) was highest among basal-like markers. Follow-up data of 19 patients were available. Median progression-free survival was 15.5 months. In 12 patients (63.2%), local recurrence and/or distant metastasis developed (median time to recurrence and/or metastasis, 14.0 months). Conclusions:, CNC has distinctive morphological features, which mostly exhibit a basal-like immunophenotype and poor prognosis. CNC is a typical representative of basal-like breast cancer. [source] Impact of treatment-related liver toxicity on the outcome of HCV-positive non-Hodgkin's lymphomas,AMERICAN JOURNAL OF HEMATOLOGY, Issue 1 2010Luca Arcaini We studied 160 Hepatitis C virus (HCV)-positive patients with NHL (59 indolent NHL, 101 aggressive). Median age was 67 years. HCV-RNA was present in 146. HBsAg was positive in seven patients. At diagnosis, ALT value was above UNL in 67 patients. One hundred and twenty patients received an anthracycline-based therapy, alkylators, 28 received chemotherapy plus rituximab. Cytotoxic drugs dose was reduced in 63 patients. Among 93 patients with normal ALT at presentation, 16 patients developed WHO grade II,III liver toxicity. Among 67 patients with abnormal ALT, eight patients had a 3.5 times elevation during treatment. Among 28 patients treated with rituximab and chemotherapy, five patients (18%) developed liver toxicity. Thirty four patients (21%) did not complete treatment (eight for liver toxicity). Median progression-free survival (PFS) for patients who experienced liver toxicity is significantly shorter than median PFS of patients without toxicity (respectively, 2 years and 3.7 years, P = 0.03). After a median F-UP of 2 years, 32 patients died (three for hepatic failure). A significant proportion of patients with HCV+ NHL develop liver toxicity often leading to interruption of treatment. This could be a limit to the application of immunochemotherapy programs. HCV+ lymphomas represent a distinct clinical subset of NHL that deserves specific clinical approach to limit liver toxicity and ameliorate survival. Am. J. Hematol., 2010. © 2009 Wiley-Liss, Inc. [source] A PILOT STUDY OF PREOPERATIVE AND POSTOPERATIVE CHEMOTHERAPY IN PATIENTS WITH OPERABLE GASTRIC CANCER: AUSTRALASIAN GASTROINTESTINAL TRIALS GROUP STUDY 9601ANZ JOURNAL OF SURGERY, Issue 4 2007Michael Findlay Background: With poor cure rates in gastric cancer using surgery alone, the safety, efficacy and feasibility of preoperative and postoperative chemotherapy was investigated. Methods: Patients with advanced but operable gastric or cardio-oesophageal adenocarcinoma were staged using endoscopy, computed tomography scan and laparoscopy. If considered potentially resectable, they received chemotherapy (epirubicin, cisplatin and 5-fluorouracil) for 9 weeks before and after surgery. Results: Of 59 participants entered, two were found to have metastatic disease and were excluded from the analysis. Of the participants, 10 were women and 47 men; their median age was 58 years (range 27,83 years) and median performance status 0 (range 0,1). Two of the 57 participants commencing chemotherapy did not undergo surgery (one sudden death, one new liver metastases). Grade 3 and 4 preoperative and postoperative toxicity rates were, respectively, neutropenia 22 and 18%, emesis 12 and 14% and other non-haematological toxicity <10 and <10%. Of the 55 who underwent surgery, 40 had apparently curative resections (clear or positive microscopic margins), 2 died after surgery (anastomotic leak, sepsis) and 16 had postoperative complications. Of these, 27 participants commenced postoperative chemotherapy and 21 completed it. Median progression-free survival and overall survival were 19.6 and 22 months, respectively. Conclusion: Epirubicin, cisplatin and protracted venous infusion of 5-fluorouracil chemotherapy was well-tolerated in the preoperative setting and did not appear to increase complication rates of surgery for advanced and operable stomach cancer. These findings demonstrate the feasibility of this strategy in the Australasian clinical setting and are in keeping with the results of a recently reported randomized trial, which demonstrated a significant survival advantage using this chemotherapy regimen. [source] Prognostic role of insulin-like growth factor receptor-1 expression in small cell lung cancerAPMIS, Issue 12 2009MYUNG HEE CHANG Insulin-like growth factor receptor-1 (IGFR-1) is a cellular membrane receptor which is overexpressed in many tumors and seems to play a critical role in anti-apoptosis. The insulin-like growth factor binding protein-3 (IGFBP-3) is known as a growth suppressor in multiple signaling pathways. The aim of this study was to determine IGFR-1 and IGFBP-3 expression in small-cell lung cancer (SCLC) and analyze the prognostic value in patients with SCLC. We analyzed IGFR-1 and IGFBP-3 expression in 194 SCLC tissues by immunohistochemical staining. Correlative analyses between IGFR-1 and IGFBP-3 expression in SCLC and clinicopathologic factors were performed. A total of 117 patients had extensive disease (ED) (60.3%) and 77 had limited disease (39.7%). With the median follow-up duration of 49.5 months (24,82 months), the median progression-free survival (PFS) and overall survival (OS) were 7.2 months [95% confidence interval (CI): 6.4,8.0 months] and 14.4 months (95% CI: 12.7,16 months), respectively. IGFR-1 expression was observed in 154 of the 190 tumor tissues, whereas there was no IGFBP-3 expression. Multivariate analysis showed that stage (p < 0.001), response rate (p < 0.001), and lactate dehydrogenase (LDH) levels (p < 0.001) were the independent prognostic factors for PFS, and age (p = 0.014), LDH level (p < 0.001), and stage (p < 0.001) for OS. The IGFR-1 positivity was not associated with PFS or OS in the entire cohort. Subgroup analysis revealed that OS was significantly longer in patients with IGFR-1-positive tissue than IGFR-1-negative tissue in SCLC-ED (p = 0.034). These results suggest that IGFR-1 expression may be useful as a prognostic marker in patients with SCLC-ED. [source] Recurrent ovarian cancer: Treatment with pegylated liposomal doxorubicin; a Westmead Cancer Care Centre experienceASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, Issue 1 2010Rachel F DEAR Abstract Aim: To describe the overall survival, progression-free survival, response rate and toxicity of pegylated liposomal doxorubicin (PLD) in recurrent ovarian cancer. Methods: A retrospective study of 45 patients with recurrent or progressive ovarian cancer was conducted at the Westmead Cancer Care Centre. Patients received PLD at a starting dose of 30,50 mg/m2 every 4 weeks. Results: A total of 43 patients were included for analysis. The starting dose was 40 mg/m2 in 67% of cases, and 21 % had a dose increase. A median of 2 cycles (mean 3, range 1,7) was given. All patients were assessable for response and 77% stopped treatment due to progressive disease. The overall response rate to PLD assessed by CA-125 criteria was 14 percent (six of 43 patients). Five patients (12 percent) were from the potentially platinum-sensitive group and one (2 percent) was from the platinum-resistant group. The overall median progression-free survival was 52 days (2 months), which was greater in the platinum-sensitive than in the platinum-resistant group (4.4 months vs 1.7 months, respectively, P = 0.030). The median overall survival was 296 days (10.6 months) with a trend for this to be longer in the platinum-sensitive than in the platinum-resistant group (13 vs 9 months, P = 0.393). Overall 25 percent of patients had grade 2 or 3 toxicity. Conclusion: The benefit of PLD in platinum-resistant recurrent ovarian cancer is small and the treatment has considerable toxicity. These data support the need to establish whether chemotherapy in this setting has any favorable effect on quality of life. The Australian New Zealand Gynaecological Oncology Group is currently addressing this question in a large prospective study measuring both the subjective and objective benefit (response and survival) of palliative chemotherapy in platinum-resistant or refractory ovarian cancer in Australia. Clinicians are urged to enter their patients in this study to address this important question. [source] Randomized trial of paclitaxel versus pegylated liposomal doxorubicin for advanced human immunodeficiency virus-associated Kaposi sarcomaCANCER, Issue 16 2010Evidence of symptom palliation from chemotherapy Abstract BACKGROUND: Paclitaxel and pegylated liposomal doxorubicin (PLD) are active cytotoxic agents for the treatment of human immunodeficiency virus (HIV)-associated Kaposi sarcoma (KS). A randomized trial comparing the efficacy and toxicity of paclitaxel and PLD was performed, and the effects of therapy on symptom palliation and quality of life were determined. METHODS: Patients with advanced HIV-associated KS were randomly assigned to receive paclitaxel at a dose of 100 mg/m2 intravenously (iv) every 2 weeks or PLD at a dose of 20 mg/m2 iv every 3 weeks. The KS Functional Assessment of HIV (FAHI) quality of life instrument was used before and after every other treatment cycle. RESULTS: The study included 73 analyzable patients enrolled between 1998 and 2002, including 36 in the paclitaxel arm and 37 in the PLD arm; 73% of patients received highly active antiretroviral therapy (HAART) and 32% had an undetectable viral load (<400 copies/mL). Treatment was associated with significant improvements in pain (P = .024) and swelling (P < .001). Of the 36 patients who reported that pain interfered with their normal work or activities at baseline, 25 (69%) improved. Of the 41 patients who reported swelling at baseline, 38 (93%) improved. Comparing the paclitaxel and PLD arms revealed comparable response rates (56% vs 46%; P = .49), median progression-free survival (17.5 months vs 12.2 months; P = .66), and 2-year survival rates (79% vs 78%; P = .75), but somewhat more grade 3 to 5 toxicity for paclitaxel (84% vs 66%; P = .077). CONCLUSIONS: Treatment with either paclitaxel or PLD appears to produce significant improvements in pain and swelling in patients with advanced, symptomatic, HIV-associated KS treated in the HAART era. Cancer 2010. © 2010 American Cancer Society. [source] Combined treatment with pegylated interferon,,-2a and dacarbazine in patients with advanced metastatic melanomaCANCER, Issue 6 2008A phase 2 study Abstract BACKGROUND. Dacarbazine (DTIC) and pegylated interferon (IFN),,-2a have both demonstrated some efficacy as single agents in metastatic melanoma. To the authors' knowledge, the current study is the first to test a combination of these 2 agents in a phase 2 trial. METHODS. Twenty,eight patients with stage IV melanoma without brain metastases were treated with DTIC (at a dose of 850 mg/m2 every 3 weeks) combined with weekly pegylated IFN,,-2a at a dose of 180 ,g. The study was initiated to evaluate the efficacy and tolerability of the combination. The primary study endpoint was objective response. RESULTS. Twenty,five patients were evaluable for response. Two patients (8.0%) achieved a complete response that continued for >480 days and 746 days, respectively. Four patients (16.0%) demonstrated a partial response, and another patient experienced stable disease. Six of 7 nonprogressive patients had either not received treatment or had not developed disease progression during adjuvant IFN treatment for stage II/III disease. The median duration of response was 236 days, the median progression-free survival was 56 days, and the overall survival time was 403 days. Few grade 3 toxicities and only 1 grade 4 toxicity were observed (according to National Cancer Institute Common Toxicity Criteria). CONCLUSIONS. The combination of DTIC and pegylated IFN,,-2a was found to be well tolerated in patients with metastatic melanoma. The response rate of 24%, including 2 long-lasting complete responses, is encouraging, but must be confirmed in larger trials. Cancer 2008. © 2008 American Cancer Society. [source] Randomized phase 2 study of irinotecan plus cisplatin versus gemcitabine plus vinorelbine as first-line chemotherapy with second-line crossover in patients with advanced nonsmall cell lung cancerCANCER, Issue 2 2008Ji-Youn Han MD Abstract BACKGROUND. The current study was performed to compare the nonplatinum-based combination of gemcitabine and vinorelbine (GV) with the combination of irinotecan and cisplatin (IP) as first-line chemotherapy with second-line crossover in patients with advanced nonsmall cell lung cancer (NSCLC). METHODS. Patients were randomly assigned to received either irinotecan at a dose of 65 mg/m2 plus cisplatin at a dose of 30 mg/m2 (Arm A) or gemcitabine at a dose of 900 mg/m2 plus vinorelbine at a dose of 25 mg/m2 (Arm B), each of which was administered on Days 1 and 8 every 3 weeks as the first-line therapy followed by crossover at the time of disease progression. RESULTS. A total of 146 patients were enrolled (75 patients in Arm A and 71 patients in Arm B); 138 patients were evaluable for tumor response and toxicity. During first-line therapy, IP was found to result in more grade 2+ nausea and vomiting (toxicity was graded according to the National Cancer Institute Common Toxicity Criteria [version 2.0]) (41% vs 12%; P = .0001) and alopecia (36% vs 10%; P = .0003). Pneumonitis was noted only with GV therapy (7% vs 0%; P = .058). During second-line therapy, IP was found to result in more grade 3 diarrhea (17% vs 2%; P = .039) and GV featured more cases of grade 3+ neutropenia (78% vs 40%; P = .0003). IP tended to generate more tumor responses (38% vs 26% as first-line therapy, and 30% vs 13% as second-line therapy) compared with GV. IP also demonstrated a favorable trend in median progression-free survival (4.6 months vs 3.8 months as first-line therapy and 4.5 months vs 2.6 months as second-line therapy) and overall survival (15.9 months vs 13.1 months; P = .3), but this difference was not statistically significant. The majority of patients who were refractory to IP also failed to respond to GV in the second-line setting. CONCLUSIONS. The platinum-based IP regimen appeared to be superior to the GV combination in terms of response rate. However, given the similar survival and better tolerability of the nonplatinum GV regimen, either treatment sequence would appear to be acceptable for the treatment of patients with advanced NSCLC. Cancer 2008. © 2008 American Cancer Society. [source] Multi-institutional phase II study of temozolomide administered twice daily in the treatment of recurrent high-grade gliomas,CANCER, Issue 5 2008Casilda Balmaceda MD Abstract BACKGROUND. The prognosis for patients with recurrent high-grade gliomas is poor and treatment options are limited. Current chemotherapeutic regimens can improve clinical outcomes, but extend survival by only a few months. Temozolomide is a methylating agent that is typically administered once daily. Because preclinical studies suggested that a twice-daily dosing schedule might be more effective, the safety and efficacy of twice-daily dosing of temozolomide were studied in patients with recurrent gliomas at their first, second, or third recurrence. METHODS. This multi-institutional trial enrolled 120 patients with recurrent glioblastoma multiforme (GBM), anaplastic astrocytoma (AA), or anaplastic oligodendroglioma (AO). An initial oral dose of 200 mg/m2 of temozolomide was followed by 9 consecutive doses of 90-mg/m2 every 12 hours. Treatment cycles were repeated every 28 days. Doses were escalated to 100 mg/m2 twice daily in the absence of unacceptable toxicity or were reduced if unacceptable toxicity occurred. RESULTS. For GBM, AA, and AO patients, respectively, the median progression-free survival (PFS) was 4.2 months, 5.8 months, and 7.7 months, whereas the median overall survival (OS) was 8.8 months, 14.6 months, and 18 months. The overall response rate (partial and complete) for the GBM, AA, and AO patients was 31%, 46%, and 46%, respectively. Grade 3/4 toxicities included neutropenia (1.1%), thrombocytopenia (3.6%), and anemia (0.3%) (graded according to the World Health Organization grading system). CONCLUSIONS. Twice-daily dosing may enhance the efficacy of temozolomide in the treatment of recurrent gliomas without increasing toxicity. This regimen compares favorably with other dosing schedules of temozolomide reported in the literature. Cancer 2008. © 2008 American Cancer Society. [source] High-dose ifosfamide with mesna and granuloctye,colony-stimulating factor (recombinant human G-CSF) in patients with unresectable malignant mesotheliomaCANCER, Issue 2 2003A Southwest Oncology Group study Abstract BACKGROUND The current study was conducted to assess the activity and toxicity of high-dose ifosfamide and mesna with recombinant human granulocyte,colony-stimulating factor (rhG-CSF), given in an outpatient setting, in the treatment of patients with unresectable malignant mesothelioma. METHODS Between September 1994 and September 1996, 41 patients with histologically verified, unresectable malignant mesothelioma were registered, 38 of whom were analyzable (2 were ineligible and 1 was nonanalyzable). Patients received intravenous ifosfamide at a dose of 2.8 g/m2 over 3 hours (total dose of 14 g/m2), plus mesna at a dose of 0.56 g/m2 prior to and at 4 hours and 8 hours after ifosfamide infusion daily for 5 days every 21 days. rhG-CSF at a dose of 5 ,g/kg/day was administered subcutaneously on days 6,15. RESULTS Response assessment could be determined adequately in 21 patients. Two patients obtained responses; 1 was a confirmed partial response (3%; 95% confidence interval [95% CI], 0,14%) and 1 was an unconfirmed response (3%; 95% CI, 5,14%). Eleven patients had stable disease (29%), 7 patients developed disease progression (18%), 1 patient had an early death (3%), and 17 patients had inadequate assessment (45%). At the time of last follow-up, 36 of the 38 eligible patients had developed disease progression, with a median progression-free survival of 5 months (95% CI, 3,7 months) and 34 patients had died with a median survival of 7 months (95% CI, 6,9 months). Twenty-four patients (63%) and 7 patients (18%), respectively, had Grade (according to Southwestern Oncology Group Toxicity Criteria) 4 hematologic toxicities and Grade 4 nonhematological toxicities. There was one treatment-related death, the result of infection, pulmonary edema, and renal failure. CONCLUSIONS This regimen demonstrated a low overall objective response rate with substantial toxicity, and in the opinion of the authors does not warrant further investigation in the treatment of patients with unresectable malignant mesothelioma. Cancer 2003;98:331,6. © 2003 American Cancer Society. DOI 10.1002/cncr.11512 [source] Randomized phase II study of concurrent and sequential rituximab and CHOP chemotherapy in untreated indolent B-cell lymphomaCANCER SCIENCE, Issue 4 2006Michinori Ogura CHOP combined with rituximab (R-CHOP) is regarded as one of the most effective treatments for indolent B-cell non-Hodgkin lymphoma (B-NHL), however, its optimal combination schedule remains unknown. We performed a randomized phase II study to explore a more promising schedule in untreated, advanced indolent B-NHL. Patients were randomized to receive either six courses of CHOP concurrently with rituximab (Arm C), or six courses of CHOP followed by six courses of weekly rituximab (Arm S). A total of 69 patients received the concurrent (n = 34) or sequential (n = 35) regimen. Overall response rate (ORR) in Arm C was 94% (95% confidence interval [CI], 79 to 99), including a 66% complete response (CR) compared with 97% (95% CI, 85,100), including a 68% CR in Arm S. Patients in Arm C experienced more grade 4 neutropenia (85%versus 70%) and experienced more grade 3 or greater non-hematological toxicities (21%versus 12%). Both arms were tolerated well. With a median follow-up of 28.2 months, the median progression-free survival (PFS) time was 34.2 months in Arm C, and was not reached in Arm S. R-CHOP is highly effective in untreated indolent B-NHL, either concurrent or in a sequential combination. Both combination schedules deserve further investigation. (Cancer Sci 2006; 97: 305 , 312) [source] | ||||||||||||||||||||||