Temozolomide in Malignant Gliomas of Childhood: A United Kingdom Children’s Cancer Study Group and French Society for Pediatric Oncology Intergroup Study

2002 ◽  
Vol 20 (24) ◽  
pp. 4684-4691 ◽  
Author(s):  
L. S. Lashford ◽  
P. Thiesse ◽  
A. Jouvet ◽  
T. Jaspan ◽  
D. Couanet ◽  
...  
Keyword(s):  
Response Rate ◽  
Objective Response ◽  
Malignant Gliomas ◽  
High Grade Glioma ◽  
Study Cohort ◽  
High Grade ◽  
French Society ◽  
Significant Treatment ◽  
Best Response ◽  
Daily Schedule

PURPOSE: To determine the response rate of the malignant gliomas of childhood to an oral, daily schedule of temozolomide. PATIENTS AND METHODS: A multicenter, phase II evaluation of an oral, daily schedule of temozolomide (200 mg/m2 on 5 consecutive days) was undertaken in children with relapsed or progressive, biopsy-proven, high-grade glioma (arm A) and progressive, diffuse, intrinsic brainstem glioma (arm B). Evidence of activity was defined by radiologic evidence of a sustained reduction in tumor size on serial magnetic resonance imaging scans. RESULTS: Fifty-five patients were recruited (34 to arm A and 21 to arm B) and received 215 cycles of chemotherapy. Grade 3/4 thrombocytopenia was the most frequent toxic event (7% of cycles). Prolonged myelosuppression resulted in significant treatment delays and dose reductions (17% and 22% of cycles, respectively). Two toxic deaths were documented and were related to myelosuppression and sepsis in one patient and pneumonia in a second. The overall (best) response rate was 12% for arm A (95% confidence interval [CI], 3 to 28 in the study cohort, and 2 to 31 for eligible patients) and 5% and 6%, respectively, for arm B (95% CI, 0 to 26 in the study cohort, and 0 to 27 for eligible patients). Stabilization of disease was also documented and was most noteworthy for brainstem gliomas, where two patients achieved both radiologic static disease and discontinued steroid medication. CONCLUSION: Despite moderate toxicity, objective response rates to temozolomide have been low, indicating that temozolomide has minimal activity in the high-grade gliomas of childhood.

scholarly journals An Observational Study of the First Experience with Bevacizumab for the Treatment of Patients with Recurrent High-Grade Glioma in Two Belgian University Hospitals

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
M. Huylebrouck ◽  
S. Lv ◽  
J. Duerinck ◽  
A. Van Binst ◽  
I. Salmon ◽  
...  
Keyword(s):  
Phase Ii ◽  
Tumor Response ◽  
Metabolic Response ◽  
Objective Response ◽  
Progression Free Survival ◽  
High Grade Glioma ◽  
High Grade ◽  
University Hospitals ◽  
Phase Ii Trials ◽  
Antiangiogenic Effect

Background. Bevacizumab (BEV), a humanized immunoglobulin G1 monoclonal antibody that inhibits VEGF has demonstrated activity against recurrent high-grade gliomas (HGG) in phase II clinical trials.Patients and Methods. Data were collected from patients with recurrent HGG who initiated treatment with BEV outside a clinical trial protocol at two Belgian university hospitals.Results. 19 patients (11 M/8 F) were administered a total of 138 cycles of BEV (median 4, range 1–31). Tumor response assessment by MRI was available for 15 patients; 2 complete responses and 3 partial responses for an objective response rate of 26% for the intent to treat population were observed on gadolinium-enhanced T1-weighted images; significant regressions on T2/FLAIR were documented in 10 out of 15 patients (67%). A reduced uptake on PET was documented in 3 out of 4 evaluable patients. The six-month progression-free survival was 21% (95% CI 2.7–39.5). Two patients had an ongoing tumor response and remained free from progression after 12 months of BEV treatment.Conclusions. The activity and tolerability of BEV were comparable to results from previous prospective phase II trials. Reduced uptake on PET suggests a metabolic response in addition to an antiangiogenic effect in some cases with favorable clinical outcome.

Anlotinib alone or in combination with temozolomide in recurrent high-grade glioma: A retrospective study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14019-e14019
Author(s):  
Qun-ying Yang ◽  
Cheng-Cheng Guo ◽  
Zhenqiang He ◽  
Fuhua Lin ◽  
Ji Zhang ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Initial Dose ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Objective Response ◽  
High Grade Glioma ◽  
Combination Regimen ◽  
High Grade ◽  
Multikinase Inhibitor ◽  
Rano Criteria

e14019 Background: High-grade glioma (HGG) is the most common malignant brain tumor and lacks effective treatment regimen. Anlotinib is a multikinase inhibitor blocking angiogenesis and tumor cell proliferation simultaneously. This study was performed to evaluate the efficacy and safety of anlotinib alone or in combination with temozolomide (TMZ) in the treatment of recurrent HGG. Methods: This is a single-center, retrospective study. Eligible patients (pts) were diagnosed with pathologically confirmed high grades (WHO III/IV) glioma and had recurrent or progressive disease on or after prior treatment. Other key eligibility criteria included Karnofsky Performance Status (KPS) ≥ 40, aged 16 ̃75 years and having at least one measurable lesion (RANO criteria). Pts were administrated with anlotinib once daily for 14 days every 3 weeks till disease progression, intolerable toxicities or death. The initial dose was 12mg for younger pts ( < 40 years old) with KPS ≥ 60 and 10 mg for others. Combination treatment was allowed if previous TMZ was effective and tolerable. TMZ was administered on dose-dense schedule (150mg/m2, QD, d1-d7 and d15-d21 every 28 days) or metronomic schedule (25-50mg/m2 QD). The primary endpoint was progression-free survival at 6 months (PFS6m) accessed according to RANO criteria. The second endpoints included overall survival (OS), objective response rate (ORR) and disease control rate (DCR). Results: Between August 2019 and June 2020, 23 pts with HGG (15 grade IV; 8 grade III; 12 males, 11 females) were enrolled. The median age and median KPS was 42 years and 60. 16 pts have multifocal or disseminated disease. 18 pts received ≥2 lines previous treatment. At the data cutoff date on September 2020, the median duration of treatment was 9 weeks (range: 3-33). The PFS6m was 39.1% and the median PFS was 4.2 months (95% CI: 2.8, 5.6). The median OS was not reached (95% CI: NE, NE) and the OS at 12 months (OS12m) was 54.8%. 8 pts observed tumor response and 9 pts had stable disease. The ORR and DCR were 34.8% and 73.9% respectively. The results of survival analysis for subgroups were summarized in table below. Grade 1 or 2 treatment-related adverse events (TRAEs) occurred in 65.2% pts. No ≥ grade 3 TRAE was found. All hematological TRAEs occurred in patients received combination regimen. No TRAE-induced treatment termination occurred. The lower incidence of TRAE may partly attributed to that most pts (18/23) received lower initial dose (10mg) of anlotinib and the relatively shorter treatment duration. Conclusions: This study showed treatment with anlotinib alone or in combination with TMZ had promising efficacy and favorable tolerability in patients with recurrent HGG.[Table: see text]

Phase I-II Trial of Oral Cyclophosphamide, Prednisone and Lenalidomide (Revlimid®) (CPR) for the Treatment of Patients with Relapsed and Refractory Multiple Myeloma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3055-3055
Author(s):  
Donna E. Reece ◽  
Esther Masih-Khan ◽  
Arooj Khan ◽  
Saima Dean ◽  
Sharon Fung ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Dose Level ◽  
Research Funding ◽  
Response Rate ◽  
Objective Response ◽  
Median Number ◽  
Prior Therapy ◽  
Best Response ◽  
Level 3 ◽  
Grade 3

Abstract Abstract 3055 Lenalidomide (Revlimid®) and dexamethasone is an effective regimen for relapsed/refractory (rel/ref) multiple myeloma (MM) patients (pts) with an overall response rate of 60% and median time to progression of 13.4 months (Dimopoulos ME, et al. Leukemia 2009; 23: 2147-52). We combined lenalidomide with the alkylating agent combination of cyclophosphamide and prednisone—an older regimen with minimal cumulative myelosuppression and good activity as second or third line therapy (Trieu Y, et al, Mayo Clin Proc 2005; 80: 1582). The CPR regimen consisted of cyclophosphamide (CY) on days 1, 8, and 15, lenalidomide on days 1–21 and prednisone 100 mg q 2 days in a 28-day cycle. ASA 81 mg/day was given as DVT prophylaxis. Three dose levels were evaluated using a 3 × 3 dose escalation design. Thirty-two pts were entered between 11/2007-06/2009; median age was 64 (42-80) yrs, 60% were male, and immunoglobulin isotype was IgG in 19 (62%), IgA in 8 (25%) and light chain in 4 (13%) pts. Median β2-microglobulin level was 257 (92-767) nm/L, albumin 39 (34-48) g/L, creatinine 83 (50-126) μmol/L, platelet count 355 (75-479) × 109/L and ANC 2.5 (1.1-6.1) × 109/L. The median number of prior regimens was 2 (1-5). Prior therapy included: ASCT (single in 91%; double in 19%), thalidomide (28%) and bortezomib (50%). FISH cytogenetics were available in 13 pts; 1 had del 13q but none had t(4;14) or del p53. Table 1 summarizes protocol treatment delivered. Table 1. Dose level N Cyclophosphamide dose (mg/m2) Lenalidomide dose (mg) Prednisone dose (mg) Median # cycles given 1 3 150 15 100 12 (12–34+) 2 3 150 25 100 10 (9–23) 3 26 300 25 100 17 (5–28+) 1–3 (All) 32 150–300 15–25 100 19 (5–34+) Dose limiting toxicity was not observed during cycle 1 at any dose level. Grade 3–4 toxicities during the trial included: thrombocytopenia in 7 (22%) and neutropenia in 9 (29%), managed with dose reduction and/or growth factors; five episodes of febrile neutropenia occurred, all at dose level 3. In cohort 3, other grade 3–4 non-hematologic toxicities included 1 episode each of abdominal pain/bacteremia, hypokalemia, fatigue, sick sinus syndrome, cardiac amyloidosis, perforated diverticulum and 2 episodes of DVT. Two heavily pretreated pts developed 2° MDS, including 1 previously treated for lymphoma, 43 and 190 mos after the diagnosis of MM. The best response using modified EBMT criteria was documented at a median of 7 (1-26) cycles and included the following: dose level 1 (1 CR, 2 PR); dose level 2 (1 VGPR, 2 PR); dose level 3 (4 CR, 14 VGPR, 11 PR, 1 MR and 1 stable disease). At a median F/U of 16 (5-34) months, 13 pts remain on study and 18 have progressed at a median of 10 (2-23) mos; 1 was lost to F/U and 9 have died of progressive MM. The 1-year actuarial OS and PFS rates are 93% (95% CI 76–98%) and 78% (95% CI 60–89%), respectively. We conclude: 1) the combination of full doses of the agents in CPR can be given in a 28 day cycle with an acceptable safety profile; 2) the objective response rate (CR + PR + MR) in all 32 pts to date is 94%; 3) the 1-year OS of 93% and PFS of 78% compare favorably with other 3-drug combinations in rel/ref MM pts; 4) further evaluation of this regimen in newly diagnosed pts would be of interest. Disclosures: Reece: Celgene: Honoraria, Research Funding. Off Label Use: Combination of lenalidomide and cyclophosphamide and prednisone in relapsed and refractory myeloma patients. Chen:Celgene Corporation: Consultancy, Honoraria, Research Funding. Kukreti:Celgene: Honoraria.

Imatinib mesylate in the treatment of patients with recurrent high grade gliomas expressing PDGF-R

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 1526-1526 ◽  
Author(s):  
C. Marosi ◽  
M. Vedadinejad ◽  
C. Haberler ◽  
J. A. Hainfellner ◽  
K. Dieckmann ◽  
...  
Keyword(s):  
Imatinib Mesylate ◽  
Tumor Tissue ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Progression Free Survival ◽  
High Grade ◽  
Best Response ◽  
Major Response ◽  
High Grade Gliomas ◽  
Patients Experience

1526 Background: Despite noticeable progress in the treatment of high-grade gliomas (HGG), most patients experience tumor recurrence after standard treatment consisting of surgery, radiotherapy and concomitant chemotherapy. Imatinib mesylate, a tyrosine kinase inhibitor of PDGFR-α, -β, c-kit, abl and arg, has been shown to produce tumor response in patients with recurrent gliomas (Raymond ProcASCO 2004, Dresemann ProcASCO 2004&2005, Reardon Proc ASCO 2005). We treated 34 patients with recurrent HGGs showing immunohistochemical expression of “imatinib targets” in the tumor tissue with imatinib. Methods: 34 patients, 16 women, 18 men, aged from 27 to 72 years, in median 49 years with recurrent HGG (GBM n= 23, AA n=11) were treated with imatinib 400 mg/day as continuous daily oral dosing. MRI was performed every three months or at clinical suspicion of progression. The median interval from diagnosis to the start of imatinib was 12.6 months (range 4.3 to 143 months). Imatinib was the 2nd line therapy in 15 patients, 3rd line in 13 and 4th line in 6 patients. ECOG performance score at start of imatinib was 1 in 9, 2 in 21 and 3 in 4 patients, respectively.Immunohistochemical analysis was performed on formalin fixed and paraffin embedded tumor tissue with antibodies against PDGFR-α, and -β. Results: The median treatment period with imatinib was 4 months (3 weeks to 17 months). The best response achieved was major response in 2 patients, partial remission in 6, stable disease in 12 and progressive disease in 14 patients. Eleven patients were free from tumor progression after 6 months (PFS-6 32,4%). The two patients with major response improved clinically and showed no more evidence of increased metabolism as well in MRI spectroscopy as in C11-methionine PET for 13 and 17 months, respectively. One of them showed widespread PDGF-R-α expression in the tumor tissue. In all patients with objective response to imatinib, a clinical benefit was noted within the first month of treatment. Conclusions: Compared to the results of Raymond et al, we observed a higher percentage of patients with progression free survival at 6 months. Detailed analysis of imatinib targets in tumor tissue of patients treated with imatinib will be helpful to explore the potential of imatinib as treatment option for patients with HGG. No significant financial relationships to disclose.

Comparison of chemotherapy regimens for malignant gliomas with positive MGMT protein expression: Experience of 51 cases

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 12522-12522
Author(s):  
J. Zhang ◽  
Q. WU ◽  
Z. Chen
Keyword(s):  
Main Side Effect ◽  
Side Effect ◽  
Objective Response Rate ◽  
Alkylating Agent ◽  
Response Rate ◽  
Objective Response ◽  
Malignant Gliomas ◽  
Hematological Toxicity ◽  
Mgmt Protein ◽  
Agent Group

12522 Background: To compare the efficacy and toxicity of three chemotherapy regimens for MGMT positive gliomas. Methods: Fifty-one patients with histologically confirmed malignant gliomas and MGMT positive expression were enrolled in this study. The glioma tissues were examined for MGMT protein expression by immunohistochemistry. The patients were treated with: 1, regimen contained of nitrosourea (nitrosourea group) 11 cases; 2, regimen contained of temozolomide (temozolomide group) 18 cases; regimen contained of neither nitrosourea nor temozolomide(no alkylating agent group) 22 cases. Response to chemotherapy was evaluated according WHO criteria, and toxicity was evaluated according National Cancer Institute (NCI) criteria. Results: The overall objective response rate (CR + PR) for 51 cases with MGMT position gliomas was 20%, and disease control rate (CR+PR+SD) was 59%. The objective response rate and disease control rate in nitrosourea group, temozolomide group, and no alkylating agent group were 0%,18.2%,16.7% and 61.1%,31.8%,77.3%, respectively. There was significant difference between no alkylating agent group and nitrosourea group (P<0.05). Hematological toxicity and nausea/vomiting were main side-effect observed in nitrosourea group. While there was comparative lower incidence of side-effect in temozolomide group. Hematological toxicity, nausea/vomiting, and alopecia were main side-effect observed in no alkylating agent group. Though there was higher incidence of 3–4 grade hematological toxicity in this group, but it could recovered by oneself in one week or through treatment with G-CSF for 3–5 days. Conclusions: Regimen contained no alkylating agent group can obtain higher response rate and thus is worth of recommending to patients with MGMT positive gliomas. However, since modest response rate and good toleration, regimen with temozolomide shouldn’t be given up in MGMT position gliomas. Nevertheless, It is necessary to discover more efficiency way of using temozolomide. Nitrosourea should not be recommended to MGMT position glioma patients. No significant financial relationships to disclose.

Bevacizumab plus irinotecan therapy in relapsed, heavily pre-treated malignant glioma: A case series

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 12500-12500 ◽  
Author(s):  
D. M. Friedland ◽  
S. A. Ali ◽  
A. Ahmad ◽  
M. Rahman ◽  
G. Bejjani ◽  
...  
Keyword(s):  
Malignant Glioma ◽  
Performance Status ◽  
Objective Response ◽  
Malignant Gliomas ◽  
Case Series ◽  
Capillary Density ◽  
High Grade ◽  
Ecog Performance Status ◽  
Who Grade ◽  
Topoisomerase 1

12500 Background: Endothelial proliferation has been recognized as a marker of high grade or aggressive glioma in several grading classifications and it has been demonstrated that the degree of microvascularity as assessed by the endothelial cell/capillary density correlates well with the biologic aggressiveness of these tumors. These features suggest that high grade gliomas are a suitable target for angiogenesis inhibiting therapies. Bevacizumab (B) is a humanized IgG1 monoclonal antibody to VEGF that has been shown to have activity in malignant gliomas when combined with irinotecan (CPT-11), a topoisomerase 1 inhibitor. Methods: We report a case series of 10 patients with recurrent, heavily pre-treated malignant glioma who were treated with the combination of B and CPT-11. Nine patients had WHO grade 4 tumors while one had a grade 3 lesion. All patients had failed standard therapy with primary resection followed by adjuvant chemotherapy and radiation. Most had also failed additional resection, chemotherapy and radiation after their initial relapse. The mean number of failed therapies in addition to adjuvant therapy prior to starting B and CPT-11 was 3 (range 1–6) and the median ECOG performance status was 2 (range 1–3). Nine patients were started on B at a dose of 5 mg/kg every 2 weeks and were given CPT-11 at a dose of 125 mg/m2 every week for 3 weeks with 1 week off. The tenth patient received B at a dose of 10 mg/kg but with CPT-11 at 125 mg/m2 every 2 weeks. Results: This regimen was well tolerated with no CNS hemorrhages or >grade 1 bleeding. One patient had treatment held for repair of an anal fissure but then had it restarted. One patient had a DVT while on therapy. The objective response rate was 80% (8 PR and 2 SD).The median progression- free interval on treatment is 25 weeks with 5 patients still having a response at the time of this report. In patients with progressive disease, the median time to progression is 25 weeks. The median overall survival has not been reached, and exceeds 6 months. There has been one death due to disease progression. Conclusion: The combination of B and CPT-11 is safe and has excellent activity even in this relapsed, heavily pre-treated population of patients with high grade malignant glioma, most of whom would not be candidates for clinical trials. No significant financial relationships to disclose.

Efficacy of protracted dose-dense temozolomide (TMZ) in patients with progressive high-grade glioma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e13018-e13018
Author(s):  
M. U. Abacioglu ◽  
H. B. Caglar ◽  
P. F. Yumuk ◽  
Z. Akgun ◽  
B. M. Atasoy ◽  
...  
Keyword(s):  
Study Drug ◽  
High Grade Glioma ◽  
Median Number ◽  
High Grade ◽  
Female Ratio ◽  
Best Response ◽  
Group 2 ◽  
Grade 3 ◽  
Dose Dense ◽  
Group 1

e13018 Background: The study was aimed to evaluate the efficacy of TMZ on a protracted dose-dense schedule after standard 5-day TMZ regimen in patients with progressive high-grade glioma. Methods: In this phase II prospective study, patients who had progression on standard 5-day TMZ for recurrence (group 1) or recurrence after concurrent radiotherapy+TMZ and ≥ 2 cycles of adjuvant TMZ (group 2) for high-grade glioma received TMZ 100 mg/m2× 21 q28 days until progression according to MacDonald's criteria. Patients were included in the study after ethical committee approval and written informed consent. The primary end-point was 6 months PFS. Secondary end-points were OS and toxicity. Results: Between October 2006 and October 2008, 25 patients were included in the study. Nine of the patients were group 1 and 16 of them were group 2. Male/female ratio was 18/7. The median age was 50 (range, 18–70) and median KPS score was 80 (range, 50–100). The histopathology was glioblastoma in 18 and grade 3 glioma (anaplastic astrocytoma, anaplastic oligoastrocytoma or anaplastic oligodendroglioma) in 7. The median cycles of 5-day TMZ received before study entry was 6 (range, 2–18) in group 1 and 6 (2–7) in group 2. With a median follow up of 6 months (1–14 months) the median number of 21-day TMZ cycles received was 2 (range, 1–8). Radiological evaluation could not be performed in 5 patients because of early clinical progression. The best response during treatment was partial response in 2 (8%), stable disease in 9 (36%), and progression in 9 (36%) out of 20 patients assessed. The median time to progression was 2 months (1–8 months) and 6 months PFS rate was 11%. The median OS time was 8 months and 1 year OS rate was 38%. Out of 80 cycles received there was no anemia; 5 (6%) grade 1, 8 (10%) grade 2, 2 (3%) grade 3 leucopenia; 1 (1%) grade 1, 2 (3%) grade 2, 1 (1%) grade 3, 1 (1%) grade 4 thrombocytopenia; 9 (11%) grade 1, 7 (9%) grade 2, 32 (40%) grade 3, and 11 (14%) grade 4 lymphopenia. Study was terminated in 2 patients (one with grade 4 thrombocytopenia and the other with grade 4 hepatic toxicity). There was no dose reduction in the study drug due to toxicity. Conclusions: Protracted dose-dense TMZ after 5-day schedule for recurrent or progressive disease has modest efficacy with tolerable toxicity. No significant financial relationships to disclose.

FCgamma Receptor Polymorphisms Do Not Influence the Outcome of Treatment with Rituximab Followed by Active Immunotherapy with Mitumprotimut-T (FavId®, Id-KLH).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3416-3416 ◽  
Author(s):  
David G. Maloney ◽  
Barbara Pender ◽  
Erin McCarthy ◽  
Daniel P. Gold
Keyword(s):  
Response Rate ◽  
Single Agent ◽  
Objective Response ◽  
Response To Therapy ◽  
Phase Iii ◽  
Active Immunotherapy ◽  
Patient Specific ◽  
Best Response ◽  
Response To Chemotherapy

Abstract Background: Patient specific active idiotype immunotherapy with immunoglobulin idiotype is a promising new therapy for follicular NHL. Response to therapy may include both humoral and cellular anti-idiotypic immunity, but it is not clear which is most important. Prior studies have suggested that immunoglobulin FCgammaRIIIa (FCgRIIIa) polymorphisms at position 158 valine (V) or phenylalanine (F) effect the response to treatment with rituximab as well as outcomes from idiotype immunotherapy following objective response to chemotherapy. Here we present data assessing the correlation of FCgRIIIa polymorphisms and outcomes from idiotype immunotherapy following treatment with rituximab. Treatment: We determined the FCgRIIIa genotype using a SSCP method with genomic DNA isolated from 55 rituximab-naïve patients treated on a Phase II trial of mitumprotimut-T (FavId®, Id-KLH) (Koc et al, Blood, 2006; 108: #691). Four patients who progressed following rituximab and therefore did not receive mitumprotimut-T were excluded from this analysis. All 55 patients in this analysis had follicular NHL with a median age of 55 years. Thirty five patients were treatment naïve and 20 had relapsed following prior chemotherapy. Patients received rituximab (375mg/m2 i.v. weekly x 4) and those with stable or responding disease assessed at Week 11 received Id-KLH (1 mg s.q. monthly x 6) starting on Week 12 along with Leukine® (sargramostim, GM-CSF, 250 mcg, s.q.) on Days 1–4. Pts continued to receive booster injections on a reduced schedule, every other month x6 then quarterly thereafter, until disease progression. Radiological scans were performed every 3 months for the first 2 years of follow up, then every 6 months thereafter and reviewed centrally. Objective response and time to tumor progression (TTP) were assessed using modified IWG criteria (Cheson et al, J Clin Oncol1999; 17:1244). Response at 3 months, best response, TTP and progression free survival (PFS) at 1 year and 3.5 years were all assessed with respect to FCgRIIIa genotypes. Results: DNA was isolated from all 55 patients and successfully analyzed by SSCP for polymorphisms at position 158 of FCgRIIIa. Nine of 55 patients were V/V (16%), 27 were F/F (49%) and 19 were heterozygous V/F (35%). Overall, the 3 month response rate CR+PR) was 31/55 (56%) and the best overall response rate was 39/55 (71%). The 3 month response (post rituximab) was 5/9 (56%) for V/V, 9/19 (47%) for V/F and 17/27 (63%) for F/F patients. Best response was 6/9 (67%) for V/V, 12/19 (63%) for V/F and 21/27 (78%) for F/F patients. Median TTP was 19.5 months for V/V, 22.3 months for V/F and 18 months for F/F patients. The PFS at 1 year post initiation of rituximab was 57% for V/V, 61% for VF and 68% for FF patients while at the median follow-up of 3.5 years the PFS was 31% for V/V, 42% for V/F and 31% for F/F patients. Conclusions: FCgRIIIa polymorphisms were not associated with response rate or time to progression following a treatment program consisting of single agent rituximab followed by idiotype vaccination with mitumprotimut-T in rituximab-naïve patients. Results from an ongoing randomized Phase III study will assess the efficacy of this combined therapy, but these data suggest that long term PFS in patients receiving an idiotype vaccine following rituximab may rely more on a cell mediated immune response rather than a humoral response to idiotype.

Phase II Trial of Irinotecan in Children With Relapsed or Refractory Rhabdomyosarcoma: A Joint Study of the French Society of Pediatric Oncology and the United Kingdom Children's Cancer Study Group

2007 ◽  
Vol 25 (4) ◽  
pp. 356-361 ◽  
Author(s):  
Gilles Vassal ◽  
Dominique Couanet ◽  
Elizabeth Stockdale ◽  
Anne Geoffray ◽  
Birgit Geoerger ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Single Agent ◽  
Objective Response ◽  
Median Number ◽  
Tumor Burden ◽  
French Society ◽  
Heavily Pretreated ◽  
Grade 3 ◽  
Multiagent Chemotherapy

PurposeThis phase II study was designed to evaluate the efficacy of irinotecan administered intravenously once every 3 weeks in pediatric patients with recurrent or refractory rhabdomyosarcoma.Patients and MethodsA total of 35 patients younger than age 20 years, with refractory or relapsed rhabdomyosarcoma for which standard treatments have failed, received irinotecan at 600 mg/m2administered as a 60-minute infusion every 3 weeks. Concomitant treatments included atropine for cholinergic symptoms, loperamide for diarrhea at the first liquid stool, and preventive antiemetic treatment. Tumor response was assessed every two cycles until progression according to WHO criteria.ResultsThe best overall response rate to irinotecan was 11.4% (95% CI, 3.2 to 26.7%; 2.9% complete responses, 8.5% partial responses) from all patients recruited. The median times to progression and survival were 1.4 and 5.8 months, respectively. A total of 112 cycles were administered, with a median number of two cycles per patient (range, 1 to 16). The most common grade 3/4 toxicities were neutropenia (46%), abdominal pain or cramping (17%), cholinergic syndrome (14%), nausea/vomiting (11%), anemia (11%), thrombocytopenia (9%), and diarrhea (6%).ConclusionIn heavily pretreated children with a high tumor burden who have been treated with multiagent chemotherapy, irinotecan administered intravenously as a single agent, at 600 mg/m2every 3 weeks, showed an interesting objective response rate and a good tolerance profile in rhabdomyosarcoma.

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