scholarly journals Etoposide in acute nonlymphocytic leukemia. Australian Leukemia Study Group

Blood ◽  
1990 ◽  
Vol 75 (1) ◽  
pp. 27-32 ◽  
Author(s):  
JF Bishop ◽  
RM Lowenthal ◽  
D Joshua ◽  
JP Matthews ◽  
D Todd ◽  
...  
Keyword(s):  
Older Patients ◽  
World Health ◽  
Hematologic Toxicity ◽  
Acute Nonlymphocytic Leukemia ◽  
Consolidation Therapy ◽  
Who Grade ◽  
Remission Duration ◽  
Grade 3 ◽  
Additional Clinical Benefit ◽  
Health Organization

Previously untreated patients with acute nonlymphocytic leukemia (ANLL) aged 15 to 70 years were randomized to either cytosine arabinoside 100 mg/m2/d continuous intravenous (IV) infusion days 1 through 7, daunorubicin 50 mg/m2/d IV days 1 through 3 (7–3), or the same drugs intensified with etoposide 75 mg/m2/d IV days 1 through 7 (7–3–7) as induction therapy. Patients achieving complete remission (CR) received two courses of consolidation therapy (5–2 or 5–2–5) followed by maintenance therapy. Of 264 eligible patients, CR occurred in 56% of 7– 3 and 59% of 7–3–7 patients; 7–3–7 significantly improved remission duration (P = .01). The median remission duration was 12 months for 7–3 and 18 months for 7–3–7. Survival was similar when the two arms were compared overall. Subset analysis performed to identify patients with the most benefit showed that etoposide significantly prolonged remission duration in younger patients (less than 55 years) with a median of 12 months for 7–3 and 27 months for 7–3–7 (P = .01). Survival appeared to be prolonged with 7–3–7 in patients aged less than 55 years, with a median of 9 months for 7–3 as compared with 17 months for 7–3–7 (P = .03). In older patients (aged greater than or equal to 55 years), 7–3–7 was more toxic, with significantly more severe [World Health Organization (WHO) grade 3 or 4] stomatitis (P = .02) and no additional clinical benefit. Hematologic toxicity for induction courses was similar, with granulocytopenia less than 0.5 x 10(9)/L for a median of 16 days per course for 7–3 and 15 days for 7–3–7. Hematologic toxicity was more severe for 5–2–5 consolidation courses (P = .003). Induction and consolidation therapy intensified with etoposide resulted in significantly improved remission duration but not survival.

scholarly journals Etoposide in acute nonlymphocytic leukemia. Australian Leukemia Study Group

Blood ◽  
1990 ◽  
Vol 75 (1) ◽  
pp. 27-32 ◽  
Author(s):  
JF Bishop ◽  
RM Lowenthal ◽  
D Joshua ◽  
JP Matthews ◽  
D Todd ◽  
...  
Keyword(s):  
Older Patients ◽  
World Health ◽  
Hematologic Toxicity ◽  
Acute Nonlymphocytic Leukemia ◽  
Consolidation Therapy ◽  
Who Grade ◽  
Remission Duration ◽  
Grade 3 ◽  
Additional Clinical Benefit ◽  
Health Organization

Abstract Previously untreated patients with acute nonlymphocytic leukemia (ANLL) aged 15 to 70 years were randomized to either cytosine arabinoside 100 mg/m2/d continuous intravenous (IV) infusion days 1 through 7, daunorubicin 50 mg/m2/d IV days 1 through 3 (7–3), or the same drugs intensified with etoposide 75 mg/m2/d IV days 1 through 7 (7–3–7) as induction therapy. Patients achieving complete remission (CR) received two courses of consolidation therapy (5–2 or 5–2–5) followed by maintenance therapy. Of 264 eligible patients, CR occurred in 56% of 7– 3 and 59% of 7–3–7 patients; 7–3–7 significantly improved remission duration (P = .01). The median remission duration was 12 months for 7–3 and 18 months for 7–3–7. Survival was similar when the two arms were compared overall. Subset analysis performed to identify patients with the most benefit showed that etoposide significantly prolonged remission duration in younger patients (less than 55 years) with a median of 12 months for 7–3 and 27 months for 7–3–7 (P = .01). Survival appeared to be prolonged with 7–3–7 in patients aged less than 55 years, with a median of 9 months for 7–3 as compared with 17 months for 7–3–7 (P = .03). In older patients (aged greater than or equal to 55 years), 7–3–7 was more toxic, with significantly more severe [World Health Organization (WHO) grade 3 or 4] stomatitis (P = .02) and no additional clinical benefit. Hematologic toxicity for induction courses was similar, with granulocytopenia less than 0.5 x 10(9)/L for a median of 16 days per course for 7–3 and 15 days for 7–3–7. Hematologic toxicity was more severe for 5–2–5 consolidation courses (P = .003). Induction and consolidation therapy intensified with etoposide resulted in significantly improved remission duration but not survival.

Phase II trial of carboplatin in the management of malignant mesothelioma.

1990 ◽  
Vol 8 (1) ◽  
pp. 151-154 ◽  
Author(s):  
D Raghavan ◽  
P Gianoutsos ◽  
J Bishop ◽  
J Lee ◽  
I Young ◽  
...  
Keyword(s):  
Phase Ii ◽  
Malignant Mesothelioma ◽  
Phase Ii Trial ◽  
Objective Response ◽  
World Health ◽  
Hematological Toxicity ◽  
Who Grade ◽  
Life Threatening ◽  
Grade 3 ◽  
Health Organization

Thirty-one patients with advanced malignant mesothelioma, previously untreated or having received only one prior cytotoxic regimen, were treated in a prospective, single-arm phase II trial with carboplatin (NSC 241240) at a dose of 150 mg/m2 per day intravenously (IV) for 3 days (450 mg/m2/course). One complete remission and four partial remissions were achieved, yielding an overall objective response rate of 16% (95% confidence interval [CI], 5.4% to 34%). The median duration of remission was 8 months (range, 5 to 17). Nonhematological toxicity was mild (only 12% with World Health Organization [WHO] grade 3 vomiting); 16% suffered WHO grade 3 to 4 hematological toxicity, but there were no life-threatening episodes and no treatment-related deaths. Carboplatin has modest activity against malignant mesothelioma and, because of its low toxicity, has a role in the management of this disease.

Gemcitabine as a Single Agent in the Treatment of Relapsed or Refractory Aggressive Non-Hodgkin's Lymphoma

1999 ◽  
Vol 17 (12) ◽  
pp. 3786-3792 ◽  
Author(s):  
A. Fosså ◽  
A. Santoro ◽  
W. Hiddemann ◽  
L. Truemper ◽  
N. Niederle ◽  
...  
Keyword(s):  
Partial Response ◽  
Confidence Interval ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Single Agent ◽  
World Health ◽  
Hematologic Toxicity ◽  
Grade 3 ◽  
Health Organization ◽  
Hodgkin's Lymphomas

PURPOSE: A multicenter phase II trial was conducted to evaluate the efficacy and toxicity of gemcitabine in patients with relapsed or refractory aggressive non-Hodgkin's lymphomas (NHL). PATIENTS AND METHODS: Thirty-one patients with B-cell intermediate or high-grade NHL (Working Formulation) were enrolled onto the study. The median age was 61 years, with a Karnofsky performance status of ≤ 80% in 65% of patients. Forty-eight percent had stage III or IV (Ann Arbor Classification) at study entry. Pretreatment consisted of one, two, or three chemotherapeutic regimens in nine, 11, and 11 patients, respectively. Gemcitabine 1,250 mg/m2 was administered intravenously over 30 minutes on days 1, 8, and 15 of a 28-day schedule. RESULTS: Thirty patients were assessable for efficacy, and 31 were assessable for toxicity. No complete responses were observed, but six patients showed a partial response, 11 stable disease, and 13 progressive disease. The overall response rate was 20% (95% confidence interval, 8% to 39%) for assessable patients and 19% (95% confidence interval, 8% to 34%) for the intent-to-treat analysis. The median duration of partial response was 6 months (range, 3.7 to 15+ months). Nonhematologic World Health Organization grade 3 toxicity included hepatic toxicity in four patients and infection in two. Hematologic toxicity was observed as grade 3 anemia in three patients, grade 3 leukopenia in two patients, grade 3/4 neutropenia in two patients, and grade 3/4 thrombocytopenia in six patients. CONCLUSION: The present schedule of gemcitabine displays modest efficacy and mild toxicity in pretreated aggressive NHL.

Carboplatin, etoposide, and ifosfamide as intensive chemotherapy for small-cell lung cancer.

1990 ◽  
Vol 8 (5) ◽  
pp. 899-905 ◽  
Author(s):  
I E Smith ◽  
T J Perren ◽  
S A Ashley ◽  
J Woodiwiss ◽  
G V Forgeson ◽  
...  
Keyword(s):  
Small Cell Lung Carcinoma ◽  
Small Cell ◽  
World Health ◽  
Hematologic Toxicity ◽  
Small Cell Lung ◽  
Who Grade ◽  
Cell Lung Carcinoma ◽  
Median Response ◽  
Overall Response ◽  
Grade 3

Thirty-two previously untreated, fit patients with small-cell lung carcinoma (SCLC) were treated with an intensive combination chemotherapy regimen, with the aim of prolonging survival, as follows: carboplatin 400 mg/m2 intravenously (IV) day 1, ifosfamide 5 g/m2 IV day 1 in a 24-hour infusion with mesna, and etoposide 100 mg/m2 IV days 1 to 3, repeating at 28-day intervals for six courses. Limited-disease (LD) patients were given concurrent hyperfractionated radiotherapy for the first two courses, and all patients achieving a complete remission (CR) were offered prophylactic cranial irradiation (PCI). For 18 LD patients, the overall response was 94% with 72% CRs. For 14 extensive-disease (ED) patients the overall response was 100% with 29% CRs. Median response duration for LD patients was 11.5 months and for ED patients 7.5 months. Median survival for LD patients was 19 months with a predicted 24% 2-year survival and for ED patients 9.5 months with a predicted 14% 2-year survival. Hematologic toxicity was severe with 100% developing World Health Organization (WHO) grade 3-4 neutropenia and 94% WHO grade 3-4 thrombocytopenia during treatment. Seventy-two percent of patients required a dose reduction at some stage during treatment because of neutropenic infection or thrombocytopenia requiring platelet transfusions. Despite very high response rates, this intensive regimen achieves survival results only modestly better, if at all, than those reported for less toxic conventional regimens.

scholarly journals CODEL: phase III study of RT, RT + TMZ, or TMZ for newly diagnosed 1p/19q codeleted oligodendroglioma. Analysis from the initial study design

2020 ◽  
Author(s):  
Kurt A Jaeckle ◽  
Karla V Ballman ◽  
Martin van den Bent ◽  
Caterina Giannini ◽  
Evanthia Galanis ◽  
...  
Keyword(s):  
Cox Regression ◽  
Progression Free Survival ◽  
Initial Study ◽  
Phase Iii ◽  
World Health ◽  
Newly Diagnosed ◽  
Who Grade ◽  
Phase Iii Study ◽  
Grade 3 ◽  
Health Organization

Abstract Background We report the analysis involving patients treated on the initial CODEL design. Methods Adults (>18) with newly diagnosed 1p/19q World Health Organization (WHO) grade III oligodendroglioma were randomized to radiotherapy (RT; 5940 centigray ) alone (arm A); RT with concomitant and adjuvant temozolomide (TMZ) (arm B); or TMZ alone (arm C). Primary endpoint was overall survival (OS), arm A versus B. Secondary comparisons were performed for OS and progression-free survival (PFS), comparing pooled RT arms versus TMZ-alone arm. Results Thirty-six patients were randomized equally. At median follow-up of 7.5 years, 83.3% (10/12) TMZ-alone patients progressed, versus 37.5% (9/24) on the RT arms. PFS was significantly shorter in TMZ-alone patients compared with RT patients (hazard ratio [HR] = 3.12; 95% CI: 1.26, 7.69; P = 0.014). Death from disease progression occurred in 3/12 (25%) of TMZ-alone patients and 4/24 (16.7%) on the RT arms. OS did not statistically differ between arms (comparison underpowered). After adjustment for isocitrate dehydrogenase (IDH) status (mutated/wildtype) in a Cox regression model utilizing IDH and RT treatment status as covariables (arm C vs pooled arms A + B), PFS remained shorter for patients not receiving RT (HR = 3.33; 95% CI: 1.31, 8.45; P = 0.011), but not OS ((HR = 2.78; 95% CI: 0.58, 13.22, P = 0.20). Grade 3+ adverse events occurred in 25%, 42%, and 33% of patients (arms A, B, and C). There were no differences between arms in neurocognitive decline comparing baseline to 3 months. Conclusions TMZ-alone patients experienced significantly shorter PFS than patients treated on the RT arms. The ongoing CODEL trial has been redesigned to compare RT + PCV versus RT + TMZ.

Efficacy and safety profile of gemcitabine in non-small-cell lung cancer: a phase II study.

1994 ◽  
Vol 12 (8) ◽  
pp. 1535-1540 ◽  
Author(s):  
R P Abratt ◽  
W R Bezwoda ◽  
G Falkson ◽  
L Goedhals ◽  
D Hacking ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Single Agent ◽  
Small Cell ◽  
World Health ◽  
Hematologic Toxicity ◽  
Small Cell Lung ◽  
Who Grade ◽  
Grade 3

PURPOSE The aim of this study was to evaluate the efficacy and toxicity of gemcitabine at higher doses than had been used previously in patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Eighty-four patients (65 men, 19 women; age range, 35 to 75 years; mean age, 59 years) with locally advanced or metastatic pathologically documented NSCLC were enrolled. Patients had bidimensionally measurable disease, as defined by computed tomographic (CT) scan or chest x-ray. A total of 28.6% had previously been surgically treated, while 9.5% had received radiotherapy. Fifty-three patients commenced at a dose of 1,000 mg/m2, and 31 at a dose of 1,250 mg/m2. Patients were to receive two dose escalations of 25%, provided that overall toxicity was no worse than World Health Organization (WHO) grade 1 or WHO grade 0 for platelets. Responding patients were reviewed and validated by a blinded oncology review board (ORB) of experts not involved with the study. Of the original 84 patients enrolled, 76 were assessable. RESULTS The overall response rate was 20% (95% confidence interval [CI], 11.6% to 30.8%). There were two complete responses (3%) and 13 partial responses (17%). Hematologic toxicity was negligible. WHO grade 3 WBC toxicity occurred in 0.9% of doses and WHO grade 4 in 0.1%. WHO grade 3 and 4 thrombocytopenia occurred in 0.1% and 0.1% of all doses, respectively. Nonhematologic toxicity was minor and easily controlled. Common side effects included peripheral edema, asthenia, and transient malaise. CONCLUSION The single-agent efficacy of gemcitabine is equivalent to other agents commonly used to treat NSCLC. Gemcitabine has an unusually mild side effect profile for such an active agent. The nausea and vomiting experienced with gemcitabine are mild and generally well controlled with standard antiemetics; 5-HT3 receptor antagonists are typically not required. The use of gemcitabine does not cause significant alopecia, and hematologic toxicity is modest and unlikely to require hospitalization. Gemcitabine may have a role as monotherapy in patients with inoperable NSCLC.

High complete remission rates with primary neoadjuvant infusional chemotherapy for large early breast cancer.

1995 ◽  
Vol 13 (2) ◽  
pp. 424-429 ◽  
Author(s):  
I E Smith ◽  
G Walsh ◽  
A Jones ◽  
J Prendiville ◽  
S Johnston ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Operable Breast Cancer ◽  
World Health ◽  
Tumor Diameter ◽  
Conventional Chemotherapy ◽  
Who Grade ◽  
Remission Rates ◽  
Ambulatory Pump ◽  
Grade 3 ◽  
Health Organization

PURPOSE To investigate the efficacy of continuous infusion fluorouracil (5FU) with every-3-week epirubicin and cisplatin (ECF) as primary chemotherapy instead of immediate mastectomy for patients with large, potentially operable, breast cancer. PATIENTS AND METHODS Fifty patients with large operable breast cancer, median tumor diameter 6 cm (range, 3 to 12), were treated with 5FU 200 mg/m2/d via a Hickman line using an ambulatory pump for 6 months with epirubicin 50 mg/m2 intravenously (IV) and cisplatin 60 mg/m2 IV every 3 weeks for eight courses. Subsequent surgery and/or radiotherapy was determined by clinical response. RESULTS Forty-nine patients achieved an overall response (98%; 95% confidence interval [CI], 94% to 100%), including 33 complete clinical remissions (CRs) (66%; 95% CI, 53% to 79%). Only three patients (6%) still required mastectomy. Tumor cellularity was markedly reduced on repeat needle biopsy following 3 weeks of treatment in 81% of patients versus only 36% in similar patients after conventional chemotherapy (P < .002). Severe (World Health Organization [WHO] grade 3 to 4) toxicity was rare, with nausea/vomiting being the most common, occurring in 20% of patients. CONCLUSION Primary infusional ECF appears to be more active on clinical and histopathologic grounds than conventional chemotherapy for large operable breast cancer and is well tolerated. This approach now merits randomized comparison to determine if high CR rates may translate into improved survival.

Neutrophil dynamics and death in postchemotherapy septic neutropenia

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e17579-e17579
Author(s):  
N. A. Othieno-Abinya ◽  
G. W. Kiarie ◽  
Y. Mlombe ◽  
P. Wanzala
Keyword(s):  
Renal Function ◽  
Immune Reconstitution ◽  
World Health ◽  
Who Grade ◽  
Renal Function Impairment ◽  
Background Mortality ◽  
Function Impairment ◽  
Major Predictor ◽  
Grade 3 ◽  
Health Organization

e17579 Background: Mortality rates from septic neutropenia vary between studies, ranging from 7% to 30%. We observed the mortality rate for patients hospitalized for postchemotherapy septic neutropenia was 28.6% in one of our studies. Many deaths appeared to have occurred at the time of neutrophil recovery. We attributed this to immune reconstitution inflammatory syndrome akin to what is seen in HIV/AIDS. Methods: Records of patients who died during hospitalization with septic neutropenia. Results: Twenty one patients, 14 males (67%) and 7 females (33%) were included, age range 14–67 years. Six (28.6%) had World Health Organization (WHO) grade 0 neutropenia at the time of death, none had grade 1, one (4.8%) had grade 2, one (4.8%) grade 3, and 14 (67%) had grade 4. The last absolute neutrophil count (ANC) at death ranged between 0.005 and 6.3 x 109/litre. Ten patients (47.6%) died during neutrophil upswing and 11 (52.4%) during neutrophil decline. Thirteen patients (61.9%) also had grade 4 thrombocytopenia but no death was attributed to bleeding. Five of 18 (27.8%) had WHO grade 3 renal function impairment, and six (33.3%) had grade 2 impairment. The main cause for renal function disturbance was hypotension that was usually sudden and unexplained. There was no correlation between ANC and renal function impairment (p > 0.5). Conclusions: Death from septic neutropenia could not be attributed to neutrophil dynamics and by extension immune reconstitution from this study. Neutropenia grade 4 still stood out as a major predictor of death. Larger prospective studies are required to address this issue. No significant financial relationships to disclose.

Etoposide and carboplatin in neuroblastoma: a French Society of Pediatric Oncology phase II study.

1992 ◽  
Vol 10 (10) ◽  
pp. 1592-1601 ◽  
Author(s):  
D Frappaz ◽  
J Michon ◽  
O Hartmann ◽  
E Bouffet ◽  
O Lejars ◽  
...  
Keyword(s):  
Phase Ii ◽  
Pediatric Oncology ◽  
Phase Ii Study ◽  
World Health ◽  
High Dose ◽  
Hematologic Toxicity ◽  
French Society ◽  
Who Grade ◽  
The Status ◽  
Health Organization

PURPOSE A phase II study of etoposide (VP 16) and carboplatin (CBDCA) was performed in patients with metastatic neuroblastoma (NB). The aim of the study was to find an alternative treatment for induction with different toxicities than the VP 16/cisplatin (CDDP) combination. PATIENTS AND METHODS Forty-seven patients who were from 6 months to 16 years of age, with either relapsed (29) or primary resistant (18) NB, were included in a cooperative multicenter phase II study of the French Society of Pediatric Oncology (SFOP). The schedule consisted of 5 consecutive days of VP 16 100 mg/m2/d and CBDCA 160 mg/m2/d. RESULTS The response rate for the 39 assessable patients was 43%; there were four complete remissions and 13 partial remissions. Neither the status of the patients nor the total dose of CDDP that was received previously influenced response. Hematologic toxicity was marked and caused considerable delay between courses (median interval, 39 days). In these heavily pretreated patients, 16% had a more than 50% decrease in creatinine clearance and a 22% World Health Organization (WHO) grade 2 ototoxicity. CONCLUSION This VP 16/CBDCA combination deserves further evaluation for efficacy and toxicity in newly diagnosed patients, and the combination of both drugs should be considered for high-dose therapy with bone marrow transplantation.

scholarly journals Mosaic Pattern of H3 K27M-Mutant Protein Expression in a Diffuse Midline Glioma—A Diagnostic Dilemma for the Pathologist

2021 ◽  
Author(s):  
Deepti Narasimhaiah ◽  
Bejoy Thomas ◽  
Mathew Abraham ◽  
Rajalakshmi Poyuran
Keyword(s):  
Tumor Tissue ◽  
World Health ◽  
Mutant Protein ◽  
Histone Genes ◽  
Mosaic Pattern ◽  
Diagnostic Dilemma ◽  
Who Grade ◽  
Therapeutic Implications ◽  
Health Organization ◽  
Diffuse Midline Glioma

AbstractDiffuse midline glioma, H3 K27M-mutant, is a World Health Organization (WHO) grade IV glioma arising in pons, thalamus, and spinal cord. They show mutations resulting in replacement of lysine at position 27 by methionine (K27M) of histone genes, H3F3A, HIST1H3B, and HIST1H3C. The H3 K27M mutant protein is identified in tumor tissue by immunohistochemistry. As these mutations are clonal and homogeneous, the mutant protein is normally identified in all tumor cells. Here we report a case of diffuse midline glioma with mosaic pattern of expression of H3 K27M mutant protein and discuss the diagnostic and therapeutic implications of this unusual pattern.

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