Treatment of advanced colorectal and gastric adenocarcinomas with 5-fluorouracil and high-dose folinic acid.

We report the results of an expanded trial of 5-fluorouracil (5-FU) combined with high-dose folinic acid for treatment of patients with advanced colorectal or advanced gastric adenocarcinoma. In each treatment course, the patients received both 5-FU (340 to 400 mg/m2/d by intravenous (IV) infusion for a period of 15 minutes) and folinic acid (200 mg/m2/d by IV bolus) for 5 consecutive days, with a 21-day interval between courses. Eighty-six patients with colorectal carcinoma were evaluated. The combined complete and partial response rates were 39% for 54 patients who did not receive prior chemotherapy and 22% for 32 patients who had previously received chemotherapy. Four patients who were previously resistant to 5-FU attained objective responses. The median time to disease progression for the 28 responders was 10 months. The median survival time of responders was 19.5 months, and the probability of their being alive at 2 years was 40%. Of 27 patients with gastric adenocarcinoma, 13 (48%) responded to therapy. Their median time to disease progression was 5.5 months. The median survival time of responders was 11 months, and their probability of being alive at 15 months was 30%. Toxicity was within acceptable limits. Toxic effects included stomatitis, diarrhea, conjunctivitis, skin rash, and mild myeloid hypoplasia. In a separate study, plasma concentrations of L-folates greater than 10(-5) mol/L were achieved after a rapid single IV injection of 200 mg/m2 of folinic acid. Comparisons of our results with those reported in previous studies on 5-FU administered as a single agent suggest that, in advanced colorectal and gastric adenocarcinoma, folinic acid administered in high doses enhances the effectiveness of 5-FU administered concomitantly. Furthermore, some colorectal tumors that were previously resistant to 5-FU become sensitive to this drug. The survival of the patients who responded to therapy was markedly improved over that observed in reported series of untreated patients with advanced colorectal and gastric adenocarcinomas.

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Can Allo-HSCT Improve the Poor Clinical Outcome of the “Internal Tandem Duplication” of the FLT3 Gene?

Blood ◽

10.1182/blood.v124.21.5938.5938 ◽

2014 ◽

Vol 124 (21) ◽

pp. 5938-5938

Author(s):

Paolo Bernasconi ◽

Catherine Klersy ◽

Anna Amelia Colombo ◽

Daniela Caldera ◽

Francesco Ripamonti ◽

...

Keyword(s):

Survival Time ◽

Median Time ◽

Median Survival ◽

Median Survival Time ◽

Tandem Duplication ◽

Cox Model ◽

High Dose ◽

Internal Tandem Duplication ◽

Relapse Risk

Abstract AML patients (pts) with a normal chromosome pattern and the “Internal Tandem Duplication” (ITD) of the FLT3 gene have an overall and event-free survival (OS, EFS) inferior than those of pts with a FLT3 “wild-type” gene because of a higher relapse risk, are placed in the intermediate-1 prognostic category, and when in complete remission (CR) are candidates to allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the role of allo-HSCT in ITD+ pts is still debated and a recent retrospective analysis has stated that FLT3/ITD adversely affected allo-HSCT outcome in the same direction as it does after chemotherapy. Thus, the present study was aimed to compare the OS, EFS and relapse risk of pts submitted to allo-HSCT in first CR or in initial relapse, defined by a 5-10% bone marrow blast cell percentage, with those of pts submitted to chemotherapy alone. The study cohort consisted of 54 chromosomally normal, ITD+ consecutive non-M3 AML pts who were included in 168 AML pts aged 18-66 years who came to our observation in the period January 2007-December 2013. At diagnosis median age was 48.6 years (range 18-66), 25 pts were males and 29 females. Median follow-up was 16.2 months (0.4-68.8): median follow-up for responsive pts was 7.15 months (range 0.26-27.6), for relapsed pts was 18.1 (range 1.9-68.8) and for transplanted pts was 9.1 months (range 2.9-26.8). All pts received the same induction treatment that consisted of standard Idarubicine+Ara-c “3+7” followed by two consolidation courses with high-dose Ara-c. Those who failed induction received other treatment schedules among which Fludarabine+Ara-c+Idarubicine was the most common. At the end of consolidation 38 pts were in first CR, achieved after 3+7 in 27 pts and after a second different course in 11. Sixteen pts had a resistant disease. After a median time of five months (range 1-21) 21/38 pts (55.2%) relapsed. All received a re-induction and 8/21 (38.1%) attained a second CR. Allo-HSCT was performed in a total of 23 pts: 12 first CRs, 6 second CRs and 5 initial relapses. The donor was a sibling in 7 pts, an unrelated donor in 13 and an haplo-identical donor in 3; the HSC source was the marrow in 6 pts, the peripheral blood in 16 and the cord blood (CB) in one. The Conditioning regimen was myeloblative (mainly Busulfan+Fludarabine) in 21 and non-myeloblative in 2; GvHD prophylaxis consisted of Cyclosporine A, steroids and methotrexate “short course”. The median number of CD34+ cells infused was 5.14x106/kg (1.3-12.7). All pts except that who received CB engrafted after a median time of 15 days (12-28); 21 were complete chimeras, two partial chimeras. Thirteen pts developed acute GvHD (grade I in 3 pts, grade II in 5, grade III in 2 and grade IV in 3) which totally/partially recovered after high dose steroids along with different immunosuppressive drugs in 4 and 9 pts respectively. Eleven pts developed a chronic GvHD which was the evolution of an aGvHD in 9, targeted different organs, was stable in 3 pts and completely/partially recovered in 4 and 2 pts respectively. Post-transplant relapse occurred in 3/12 first CRs, in none second CRs and in 3/5 initial relapse. The estimated response rate for CR pts submitted to allo-HSCT was 422.1 (95% CI: 262.4-679.1) versus 64.6 (95% CI: 40.7-102.6) for those submitted to chemotherapy alone with a median survival time of 7.2 months (range 5.3-8.8) versus not reached (1.9-not available); on univariable Cox model the HR of allo-HSCT pts was 37.9 (95% CI: 9.4-152.0) with p=0.0000. The estimated relapse rate for CR pts submitted to allo-HSCT was 8.6 (95% CI: 2.1-34.4) versus 44.3 (95% CI: 25.7-76.3) for those submitted to chemotherapy alone with a median survival time not reached (range not available) versus 13.2 (7.2-not available); on univariable Cox model the HR of allo-HSCT pts was 0.5 (95% CI: 0.2-1.1) with p=0.06. The estimated death rate for CR pts submitted to allo-HSCT was 28.7 (95% CI: 13.7-60.4) versus 49.7 (95% CI: 32.1-77.1) for those submitted to chemotherapy alone with a median survival time of 18.3 months (range 14.2-not available) versus 12.2 (8.8-18.9); on univariable Cox model the HR for allo-HSCT pts was 0.48 (95% CI: 0.2-1.1) with p=0.09. In conclusion, our series suggests that in ITD+ pts allo-HSCT significantly strengthens CR in pts who had already responded to conventional chemotherapy, but it presents only a trend towards significance when its superiority to prevent relapse was considered. Disclosures Castagnola: Gilead Sciences: Research Funding.

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The efficacy of gastrectomy plus chemotherapy for stage IV gastric cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.4_suppl.132 ◽

2012 ◽

Vol 30 (4_suppl) ◽

pp. 132-132 ◽

Cited By ~ 1

Author(s):

Osamu Muto ◽

Hitoshi Kotanagi

Keyword(s):

Gastric Cancer ◽

Statistical Analysis ◽

Survival Rate ◽

Survival Time ◽

Median Survival ◽

Median Survival Time ◽

Single Agent ◽

Stage Iv ◽

Palliative Surgery ◽

Stage Iv Gastric Cancer

132 Background: Metastatic gastric adenocarcinoma is an incurable condition. Despite the recently reported benefits of chemotherapies, the prognosis of advanced gastric cancer remains poor. The role of surgical resection is still debatable. Therefore, we investigated the efficacy of gastrectomy plus chemotherapy for stage IV gastric cancer. Methods: We retrospectively evaluated the efficacy of gastrectomy plus chemotherapy for treating stage IV gastric cancer. Among the 753 patients with gastric cancer treated with gastrectomy at our institute between 2003 and 2010, a total of 70 patients classified into stage IV and underwent gastrectomy with perioperative chemotherapy were included in this study. In the analysis, particular attention was paid to the prognostic factors of age, gender, tissue type, metastatic site, pre or postoperative chemotherapy, single agent or combination chemotherapy and the reason for gastrectomy (palliative surgery due to stenosis, bleeding or perforation and reduction surgery). The survival rate was calculated by the Kaplan Meier method and a statistical analysis was performed using the log-rank test. Survival was calculated from the beginning of the treatment until the last follow-up or death from any cause. Results: The median age was 65 years old. Peritoneal, lymph node and liver metastasis were 28, 23, and 13 patients respectively. Fifty-three patients had diffuse type. Gastrectomy followed by chemotherapy and chemotherapy were 53 patients. Single agent chemotherapy were 42 and combination were 28 patients. Thirty-one patients were underwent palliative surgery and 39 patients were reduction surgery. One-year survival rate of all patients was 43% and the median survival time was 19.9 months. In the statistical analysis, only reduction surgery plus chemotherapy demonstrated significant survival benefit. The median survival time was significantly greater in patients undergoing reduction gastrectomy group than in those undergoing palliative gastrectomy (25.3 versus 9.8 months; p=0.005). Conclusions: Long-term survival for patients with stage IV gastric cancer who are managed with reduction surgery and chemotherapy is achievable. Further study with a larger number of patients is warranted.

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Efficacy of SMIP-016, a novel CD37-directed biologic therapy, in human NHL tumor xenograft models

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.2565 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 2565-2565

Author(s):

D. S. Barone ◽

C. Nilsson ◽

J. Ledbetter ◽

M. Hayden-Ledbetter ◽

K. Mohler

Keyword(s):

Survival Time ◽

Median Survival ◽

Nude Mice ◽

Median Survival Time ◽

Single Agent ◽

Human Tumor ◽

Lymphocytic Leukemia ◽

Tumor Xenograft ◽

Human Tumor Xenograft ◽

Xenograft Models

2565 Background: Small Modular Immuno-Pharmaceuticals (SMIP) biopharmaceuticals belong to a novel proprietary biologic compound class that retain Fc mediated effector functions and are smaller than monoclonal antibodies. SMIP-016 is a SMIP product candidate that binds to CD37 on human B cells and has potent ADCC and apoptotic activity in vitro. CD-37 is known to be over-expressed in non-Hodgkin’s lymphoma (NHL) and chronic lymphocytic leukemia (CLL). We have evaluated the activity of SMIP-016 in established human tumor xenograft models in nude mice. Methods: Nude mice were injected subcutaneously with either Ramos or Daudi tumor cells. At approximately 7 days post tumor inoculation the mice were randomized to groups with roughly equivalent mean tumor volumes (>200mm3) and were treated with SMIP-016 or rituximab as a comparator. Groups were evaluated for median survival time (MST), tumor volume and percentage of tumor-free animals. Results: In nude mice bearing Daudi tumors, SMIP-016 treated mice showed a significant improvement in MST compared to control mice (p < 0.0001). Nude mice bearing Ramos tumors treated with SMIP-016 also demonstrated a significant enhancement in their median survival time (MST) in comparison to control mice (p < 0.0001). In addition, mice receiving SMIP-016 administered in combination with rituximab in this model demonstrated improvements in survival time over either single agent therapy alone. Conclusions: SMIP-016 is effective in treating established tumors in these human tumor xenograft models. Addition of SMIP-016 to rituximab therapy resulted in enhanced survival times compared to animals treated with rituximab alone. [Table: see text]

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Deficiency of Either Carboxypeptidase B2 or Carboxypeptidase N Exacerbated Disease Activity in a Mouse Model of Hemolytic Uremic Syndrome

Blood ◽

10.1182/blood.v128.22.3758.3758 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3758-3758

Author(s):

Lawrence L. Leung ◽

Zhifei Shao ◽

Toshihiko Nishimura ◽

Qin Zhou ◽

Laura Gigliello ◽

...

Keyword(s):

Mouse Model ◽

Hemolytic Uremic Syndrome ◽

Survival Time ◽

Median Time ◽

Median Survival ◽

Median Survival Time ◽

Conflicts Of Interest ◽

Uremic Syndrome ◽

Carboxypeptidase N ◽

C5a Anaphylatoxin

Abstract Two different basic carboxypeptidases circulate in blood - carboxypeptidase N (CPN) and proCPB2. CPN is constitutively active, while proCPB2 is a zymogen, (also termed thrombin activatable fibrinolysis inhibitor, TAFI), and is activated by the endothelial thrombin/thrombomodulin complex to CPB2. Their kinetics of substrate cleavage are distinct but both can efficiently inactivate the complement anaphylatoxins, C3a and C5a. Hemolytic uremic syndrome (HUS) is caused by Shiga toxin (stx) producing strains of E. coli and is characterized by the triad of hemolysis, thrombocytopenia and uremia. We hypothesized that in a mouse model of HUS, Cpb2-/- and Cpn-/- mice would have prolonged C5a anaphylatoxin activity thus causing disease exacerbation. HUS was induced by stx2 and LPS administration in WT, Cpn-/- and Cpb2-/- mice. In Cpb2-/- mice, median time to death was earlier (60 hours, n=15) than in WT mice (96 hours: n=42, p<0.0001), and had greater kidney and liver damage shown by increases in ALT, AST, BUN and creatinine levels at 48 hours (creatinine Cpb2-/-: 1.01 mg/dL, WT: 0.25 mg/dL; Cpb2-/- control: 0.20 mg/dL and WT control: 0.19 mg/dL; Cpb2-/- p<0.0001 vs. all other groups, n>9). An increase in hemolysis was demonstrated by reduced RBC count and hemoglobin level plus an increase in total bilirubin and LDH. Profound thrombocytopenia (Cpb2-/-: 121,000/μL vs. WT: 217,000/μL; p=ns) developed in both genotypes (control Cpb2-/-: 1,001,000/μL vs. control WT: 1,141,000/μL; p=ns but vs. either Cpb2-/- or WT with HUS, p<0.0001) and thus the HUS clinical triad was present. Histology showed tubular epithelial necrosis in the kidney ante-mortem. Administration of either toxin separately caused milder disease without the characteristics of HUS and with no observed mortality. Induction of the disease depended on co-administration of both toxins. Treatment with anti-murine C5 antibody (0.75 mg every 24 hours from 3 hours before disease initiation) improved survival of both WT and Cpb2-/- mice with a median survival time of 168 hours for both genotypes (n=11, p=0.003 and <0.0001 respectively) and normalized the outcomes between the genotypes. Cpn-/- mice also died sooner (median time to survival 81.5 hours, n=28) than WT mice (96 hours, n=42, p=0.0002). The median survival time between Cpb2-/- and Cpn-/- mice was also significantly different (60 vs. 81.5 hours, p=0.0083). This is a first direct comparison of the role of CPN vs. CPB2 in regulating C5a activity in a disease relevant mouse model. Our study suggests that both CPB2 and CPN protect against HUS by inactivation of C5a with CPB2 having a greater effect than CPN. When Cpb2+/-/Cpn+/- mice are crossed, all expected genotypes are recovered in the expected Mendelian ratios including double deficient Cpb2-/-/Cpn-/- mice. Thus absence of both plasma basic carboxypeptidases is not essential for murine life. We are currently evaluating the Cpb2-/-/Cpn-/- mice in our HUS model. Disclosures No relevant conflicts of interest to declare.

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An Expedited Palliative Radiation Protocol for Lytic or Proliferative Lesions of Appendicular Bone in Dogs

Journal of the American Animal Hospital Association ◽

10.5326/0450024 ◽

2009 ◽

Vol 45 (1) ◽

pp. 24-32 ◽

Cited By ~ 23

Author(s):

Heather M. Knapp-Hoch ◽

Janean Louise Fidel ◽

Rance K. Sellon ◽

Patrick R. Gavin

Keyword(s):

Pain Relief ◽

Survival Time ◽

Median Time ◽

Median Survival ◽

Median Duration ◽

Late Effects ◽

Median Survival Time ◽

Prognostic Indicator ◽

Bone Lesions ◽

Palliative Radiation

Fifty-eight dogs with lytic or proliferative bone lesions were treated with a radiation protocol of two 8-Gy fractions over 2 consecutive days. The protocol was well tolerated, with no increase in early or late effects over previously published protocols. Forty-three (91%) of 47 dogs responded positively to radiation, with a median time of 2 days to onset of pain relief. Median duration of pain relief was 67 days (range 12 to 503 days; mean 99±16 days). Median survival time for all dogs was 136 days (mean 179±18 days). Distal radial location was a positive prognostic indicator for survival (P=0.005).

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Phase I to II Study of Pleurectomy/Decortication and Intraoperative Intracavitary Hyperthermic Cisplatin Lavage for Mesothelioma

Journal of Clinical Oncology ◽

10.1200/jco.2005.04.6813 ◽

2006 ◽

Vol 24 (10) ◽

pp. 1561-1567 ◽

Cited By ~ 130

Author(s):

William G. Richards ◽

Lambros Zellos ◽

Raphael Bueno ◽

Michael T. Jaklitsch ◽

Pasi A. Jänne ◽

...

Keyword(s):

Relative Risk ◽

Survival Time ◽

Median Survival ◽

Median Survival Time ◽

Sodium Thiosulfate ◽

Postoperative Mortality ◽

Maximum Tolerated Dose ◽

Rank Test ◽

High Dose ◽

Epithelial Tumors

Purpose To evaluate morbidity, mortality, maximum-tolerated dose (MTD), and outcome of intraoperative intracavitary hyperthermic cisplatin lavage in patients undergoing pleurectomy for malignant pleural mesothelioma (MPM). Patients and Methods Sixty-one patients were prospectively registered. Forty-four resectable patients with MPM underwent pleurectomy, followed by a 1-hour lavage of the resection cavity with dose-escalated cisplatin (50, 100, 150, 175, 200, 225, and 250 mg/m2) at 42°C and then intravenous sodium thiosulfate (16 g/m2 over 6 hours). Survival estimates were compared using the log-rank test and proportional hazards regression. Results Median age was 71 years (range, 50 to 82 years). Twenty-four patients had epithelial tumors, and 20 had sarcomatous or mixed histology. Postoperative mortality was 11% (five of 44 patients). Dose-limiting renal toxicity occurred at 250 mg/m2, establishing the MTD at 225 mg/m2. Other morbidity included atrial fibrillation (14 of 44 patients, 32%) and deep venous thrombosis (four of 44 patients, 9%). Median survival time of all registered patients was 9 months, and the median survival time of resected patients was 13 months. Survival estimates differed significantly for resectable patients exposed to low doses (50 to 150 mg/m2; n = 9; median, 6 months) versus high doses (175 to 250 mg/m2; n = 35; median, 18 months) of hyperthermic cisplatin (P = .0019); recurrence-free interval also differed significantly (4 v 9 months, respectively; P < .0001). Low dose level (relative risk = 3.418) and nonepithelial histology (relative risk = 2.336) were independent risk factors for poor survival. Twenty patients with epithelial tumors who underwent high-dose cisplatin lavage had a 26-month median survival time. Conclusion Pleurectomy and high-dose intraoperative intracavitary hyperthermic cisplatin lavage is feasible in this patient population with restricted surgical options. An apparent dose-related survival benefit warrants further study.

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Monosomal Karyotype in MDS and Secondary AML: Do Autosomal Monosomies Have the Same Poor Prognostic Impact As Monosomy 5 and 7?

Blood ◽

10.1182/blood.v118.21.4867.4867 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4867-4867

Author(s):

Paolo Bernasconi ◽

Marina Boni ◽

Marianna Rossi ◽

Rita Zappatore ◽

Irene Dambruoso ◽

...

Keyword(s):

Disease Progression ◽

Median Time ◽

Median Survival ◽

Conflicts Of Interest ◽

Single Agent ◽

Prognostic Significance ◽

Prognostic Impact ◽

Complex Karyotype ◽

Cell Percentage ◽

Conventional Cytogenetics

Abstract Abstract 4867 Background: A monosomal karytype (MK) is defined by the presence of at least two or more distinct autosomal monosomies or an autosomal monosomy along with a structural defect. In AML this cytogenetic pattern has a very well-known poor prognostic significance independently of the specific chromosome involved. Currently, in MDS this negative prognostic influence is also emerging as recent data suggest that any monosomy in a complex karyotype (≥3 abnormalities) may have the same poor prognostic impact as monosomy 5 and 7 (−5,−7). Objectives: Thus, the principal goal of the present study was to test whether a MK further worsen the already poor prognostic influence of a complex karyotype and to establish whether autosomal monosomies have the same unfavourable prognostic impact on OS and progression free interval (PFI) as −5/−7. Methods: The eighty-five consecutive MDS patients with a complex karyotype analysed by the present study were included in a series of 631 patients who came at our observation in the period January 2000-December 2010. They were thirty-two females and fifty-three males with a median age of 65 years (range 25–85). Fifty-five patients were diagnosed as MDS and were subdivided in 3 RARS, 6 RA, 6 RCMD, 2 RCMDS, one MDS-u, 13 RAEB-1 and 24 RAEB-2. The IPSS score was intermediate-1 in 5, intermediate-2 in 23 and high in 27. During the follow-up 31 MDS patients died and 41 experienced disease progression (3 RARS, 5 RA, 4 RCMD, one MDS-u, 9 RAEB-1 and 19 RAEB-2). Thirty patients were diagnosed as AML evolved from MDS. Fifteen of them received supportive treatment only, the remaining single agent chemotherapy to control leukocytosis. Nineteen of these thirty patients died of disease related complications. Results: On conventional cytogenetics 37 patients (4 RA, 5 RCMD, one MDS-u, 8 RAEB-1, 12 RAEB-2 and 7 AML) presented a complex karyotype without monosomies and 48 (3 RARS, 2 RA, 2 RCMDS, one RCMD, 5 RAEB-1, 12 RAEB-2, 24 AML) a complex karyotype with monosomies. These two patients subgroups were comparable in terms of age, sex distribution, haemoglobin level, leukocyte or platelet counts, bone marrow blast cell percentage and IPSS score. However, median survival was 8 months (range 1–131) for patients with a complex karyotype without monosomies and 5 months (range 1–81) for those with a complex karyotype with monosomies (p=0.001). Twenty patients (54.0%) without monosomies died after a median time of 6 months (range 2–35), whereas 30 patients (62.5%) with monosomies died after a median time of 5 months (range 1–24). Disease progression was observed in 22 (59.4%) and 19 (39.5%) patients respectively (p=0.001). The 48 patients with a MK were further subdivided in those with −5/−7 versus those with other autosomal monosomies. The 23 patients with −5/−7 presented a median survival of 4 months (range 1–15) and the 25 with other monosomies presented a median survival of 5 months (range 1–81) (p=Not Significant). Fourteen −5/−7 patients died after a median time of 4 months (range 1–15) and 13 patients with autosomal monosomies died after a median time of 6 months (range 1–24). Disease progression occurred in 12 (52.1%) and 7 (28%) respectively. Conclusions: i) a MK further refines the prognostic stratification of MDS with a complex karyotype as it identifies a subgroup of patients with an extremely poor clinical outcome; ii) autosomal monosomies have an impact on disease outcome as detrimental as −5/−7. Disclosures: No relevant conflicts of interest to declare.

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Survival of multiple myeloma patients who are potential candidates for early high-dose therapy intensification/ autotransplantation and who were conventionally treated.

Journal of Clinical Oncology ◽

10.1200/jco.1996.14.7.2167 ◽

1996 ◽

Vol 14 (7) ◽

pp. 2167-2173 ◽

Cited By ~ 65

Author(s):

J Bladé ◽

J F San Miguel ◽

M Fontanillas ◽

A Alcalá ◽

J Maldonado ◽

...

Keyword(s):

Multiple Myeloma ◽

Renal Function ◽

Survival Time ◽

Median Survival ◽

Median Survival Time ◽

High Dose ◽

High Dose Therapy ◽

Dose Therapy ◽

L 62

PURPOSE To analyze the outcome of patients with multiple myeloma (MM) who were potential candidates for early high-dose therapy (HDT) intensification followed by autotransplantation from a series treated with conventional chemotherapy. PATIENTS AND METHODS From January 1985 through December 1989, 487 patients with symptomatic MM were entered onto a randomized study to compare melphalan and prednisone (MP) versus vincristine, cyclophosphamide, melphalan, and prednisone (VCMP) /vincristine, carmustine (BCNU), doxorubicin, and prednisone (VBAP). The sub-group of 77 patients who could have been candidates for early intensification with HDT followed by stem-cell support (ie, < 65 years of age, stage II or III disease, performance status < 3, and objective or partial response to initial chemotherapy) are the subjects of this report. RESULTS Seventy-seven of 487 patients could have been candidates for early intensification. The median age was 56 years (range, 27 to 64). At diagnosis, 12% had abnormal renal function, 16% hypercalcemia, and 42% serum beta 2-microglobulin level > or = 6 mg/L; 62% had stage III disease at diagnosis. Thirty-six patients were initially treated with MP and 41 with VCMP/VBAP. The median response duration to initial chemotherapy was 22 months, and the actuarial probability of being in continued first response at 5 years was 14%. After a median follow-up time of 58 months, 59 patients have died, one was lost to follow-up evaluation, and 17 are still alive 69 to 119 months after initial chemotherapy. The median survival time from initiation of treatment was 60 months and from the time when autotransplantation would be considered, 52 months. The only independent prognostic parameter for survival was renal function at diagnosis. CONCLUSION The median survival time of patients with MM who are less than 65 years of age and who respond to initial chemotherapy is 5 years. This survival duration is similar to that reported in selected series of patients given early HDT and stresses the importance of ongoing randomized trials to determine the role of HDT in the treatment of younger myeloma patients.

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Toxicity and Efficacy of Cisplatin and Doxorubicin Combination Chemotherapy for the Treatment of Canine Osteosarcoma

Journal of the American Animal Hospital Association ◽

10.5326/0410382 ◽

2005 ◽

Vol 41 (6) ◽

pp. 382-387 ◽

Cited By ~ 44

Author(s):

Ruthanne Chun ◽

Laura D. Garrett ◽

Carolyn Henry ◽

Michelle Wall ◽

Annette Smith ◽

...

Keyword(s):

Survival Time ◽

Median Survival ◽

Combination Chemotherapy ◽

Median Survival Time ◽

Single Agent ◽

Canine Osteosarcoma

Thirty-five dogs with appendicular osteosarcoma underwent amputation and chemotherapy with cisplatin and doxorubicin every 21 days for up to four cycles. Sixteen dogs completed all four cycles. Two dogs had therapy discontinued because of metastases. The remaining 17 dogs experienced toxicities necessitating protocol alteration or discontinuation. The median survival time of 300 days was not improved over previously reported single-agent protocols, but the 10 dogs that survived to a year lived a median of 510 days.

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Prevalence, Median Time and Associated Factors with the Likelihood of Initial Antidepressant Change in Treatment of Major Depressive Disorder: A Cross-Sectional Study in Qatar.

10.21203/rs.3.rs-120061/v1 ◽

2020 ◽

Author(s):

Nervana Elbakary ◽

Sami Ouanes ◽

Sadaf Riaz ◽

Oraib Abdallah ◽

Islam Mahran ◽

...

Keyword(s):

Major Depressive Disorder ◽

Depressive Disorder ◽

Survival Time ◽

Median Time ◽

Median Survival ◽

Median Survival Time ◽

Associated Factors ◽

Cox Regression ◽

Secondary Outcome ◽

Major Depressive

Abstract Background: Major Depressive Disorder (MDD) requires therapeutic interventions during the initial month after being diagnosed for better disease outcomes. International guidelines recommend a duration of 4-12 weeks for an initial antidepressant (IAD) trial at an optimized dose to get a response. If depressive symptoms persist after this duration, guidelines recommend switching, augmenting, or combining strategies as the next step. Premature discontinuation of IAD due to ineffectiveness can cause unfavorable consequences. Hence, we aimed to determine the prevalence and the patterns of strategies applied after an IAD was changed because of a suboptimal response as a primary outcome. Secondary outcomes included the median survival time on IAD before any change; and the factors that were associated with IAD change.Methods: This was a retrospective study conducted in Mental Health Services in Qatar. A dataset between January 1, 2018, and December 31, 2019, was extracted from the electronic health records. Inclusion and exclusion criteria were defined and applied. The sample size was calculated to be at least 379 patients. Descriptive statistics were reported as frequencies and percentages, in addition, to mean and standard deviation. The median time of IAD to any change strategy was calculated using survival analysis. Associated factors were examined using three cox regression models.Results: A total of 487 patients met the inclusion criteria of the study, 431 (88%) of them had an occurrence of IAD change to any strategy before end of the study. Almost half of the sample (212 (49%); 95% CI [44% - 53%]) had their IAD changed within less than or equal to 30 days. The median time to IAD change was 43 days with 95% CI [33.2 – 52.7]. Cox regression analysis showed three statistically significant factors were associated with our secondary outcome: age, un-optimization of the dose, and absence of comorbid anxiety.Conclusions: Our findings suggest that clinicians resorted to IAD change within a median time of six weeks. However, this change often occurred without optimization of the IAD dose and might be too late. Future prospective studies with adequate randomization can better investigate the median survival time on IAD and other associated factors.

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