The MYOCAN Study. A Phase II Study of Cyclophosphamide, Oncovin, Myocet™, and Prednisone Plus Rituximab (R-COMP) in the Treatment of Elderly Patients with Diffuse Large B-Cell Non-Hodgkin Lymphoma (DLBCL).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4586-4586 ◽  
Author(s):  
Massimo Federico ◽  
Martin J.S. Dyer ◽  
Maria Dolores Caballero ◽  
Claire Reilly ◽  
Eckhard Thiel
Keyword(s):  
Elderly Patients ◽  
Phase Ii ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Pegylated Liposomal Doxorubicin ◽  
Dose Intensity ◽  
Complete Response ◽  
Open Label ◽  
Dlbcl Patient ◽  
Grade 3

Abstract BACKGROUND: For more than 20 years, CHOP has been the gold standard treatment for patients with aggressive NHL. The addition of rituximab to this regimen has been shown to improve outcomes in elderly patients with advanced (Coiffier et al NEJM2002; 346:235–42). However, CHOP is often poorly tolerated by elderly patients resulting in dose reductions and consequently lower response and cure rates compared to younger patients. Myocet™ (non-pegylated liposomal doxorubicin) has an improved pharmacokinetic profile with less myelosuppression and GI toxicity and has a reduced risk of cardiotoxicity at dose levels equivalent to standard formulations of doxorubicin. METHODS: In this phase II, open label, 2-stage study, we replaced the conventional doxorubicin with Myocet™ to evaluate the response rate and safety of the R-COMP regimen (rituximab, cyclophosphamide, vincristine, Myocet™, prednisone). Previously untreated, elderly patients (≥60 yrs) with CD20+ newly diagnosed, advanced DLBCL were treated every 3 weeks with: Myocet™ 50mg/m2, cyclophosphamide 750mg/m2, vincristine 1.4 mg/m2 (max. 2mg), rituximab 375 mg/m2 (day 3 on cycle 1, day 1 thereafter) and prednisone 100mg/d d1–5 for 8 cycles. Response was assessed after 3 and 8 cycles. RESULTS: Thirty patients were enrolled in stage 1 of the study with a median age of 72 (range 61–82). At baseline 17 (56%) patients had stage III–IV disease; 60% had an intermediate or high risk (2+) International Prognostic Index score and the median LVEF was 59% (range 50–75). A total of 198 cycles of chemotherapy were given, with a median of 8 cycles (range 1–8). Of the 198 cycles administered 15 (8%) were delayed by haematological or hepatic toxicity for a median of 7 days (range 0 to 25). The relative dose intensity for the regimen was 87%, for Myocet™ it was 84%. Toxicity was mainly haematological with grade 3 or 4 neutropenia in 29% of cycles and febrile neutropenia in 4%. There was no grade 3 or 4 vomiting and a low incidence of grade 1 or 2 vomiting (3%). At the last observation the median LVEF was 55% (range 40–76), 16 patients had no change or an improved LVEF and 13 patients had a reduced LVEF. In the cohort of 24 patients evaluable for response, 15 (63%) had a complete response and an additional 7 (29%) achieved a partial response. CONCLUSIONS: These interim results suggest R-COMP is a well tolerated regimen with promising response rates in elderly patients with advanced DLBCL. Patient recruitment continues in stage 2 of the study with the aim of enrolling a total of 75 patients with a 2-year follow-up.

Final Results Of a Phase II Study Of Lenalidomide In Combination With Rituximab For The Treatment Of Indolent Non Follicular Non Hodgkin Lymphoma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4383-4383 ◽  
Author(s):  
Stefano Sacchi ◽  
Samantha Pozzi ◽  
Marina Cesaretti ◽  
Luigi Marcheselli ◽  
Gabriele Buda ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Informed Consent ◽  
Phase Ii ◽  
Conflicts Of Interest ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Open Label ◽  
Grade 3

Abstract Background Advanced-stage, relapsed indolent non follicular lymphomas (INFLs) have a relatively poor prognosis, with low complete response to conventional chemotherapy and short survival. Thus, there is a need for innovative treatment with high efficacy and a good safety profile. Lenalidomide (R®) is an immunomodulatory drug with a direct tumoricidal effect and action on T, NK and stromal cells that may enhance antibody-dependent cell mediated cytotoxicity as well as the development of specific anti-tumor immune responses. These immunologic effects may synergize with the action of rituximab (R). To test the efficacy of R® combined with R (R2), we have conducted a multi center, open label phase II clinical trial in patients (pts) with relapsed INFL. Methods Eligible pts must have indolent non follicular B-cell lymphoma relapsed after at least 2 but less than 4 prior lines of R-containing immuno-chemotherapy with measurable disease. Patients received oral R® 20 mg once daily on days 1-21. R is administered at a dose of 375 mg/m2 at day 14 of every course. Treatment is repeated every 28 days for up to 6 courses. The primary objectives of the study were to evaluate the antitumor activity of oral R® when given in combination with R and to assess the safety of R2 regimen evaluated by standard criteria (CTC-NCI 3.0). The secondary objectives were the evaluation of progression free survival (PFS) and overall survival (OS). Results From July 2010 and March 2013, 44 pts entered the protocol. Six out of 44 pts were excluded from this analysis as 2 withdrew informed consent and 4 refused to start treatment immediately after signing the informed consent. Enrolled pts (38 cases) had: 18 small lymphocytic lymphoma (SLL), 12 lymphoplasmacytic lymphoma (LPL) and 8 marginal zone lymphoma (MZL). Median age was 68 years (51-75) and 58% were male. LDH value was increased in 21% of pts and β-2-microglobulin in 75%; 51% of pts had Hb<12 g/dL and 66% had bone marrow involved (median infiltrating 40%). Of the 38 pts, 7 achieved a complete remission and 14 a partial remission with an ORR of 55%. Seven pts had a stable disease and 5 a lymphoma progression. In general, the regimen R2 was relatively well-tolerated. Grade 3-4 hematological events were observed in 22 pts. The most common adverse events were neutropenia (58%), thrombocytopenia (11%), anemia (10%) and infection (10%). Grade 3-4 non hematological events were fever (5%), dyspnea (3%), allergic reaction to R (3%), renal failure (3%) and erythema (3%). Growth factors were administered in 58% of pts. The median dose intensity was 0.94 for R and 0.98 for R®. With a median follow-up of 19 months (range 1-43), overall 6 pts died, 5 for lymphoma progression and 1 for treatment related toxicity. The 2-years OS and the 2-years PFS were shown in Figure 1. Figure 2 shows the PFS by histology. The percentage of 2-years PFS (71%) for MZL appear impressive. Conclusions The chemo-free R2 scheme as treatment for relapse INFLs produces response in about 50% of pts and remission appear durable in pts with MZL. The toxicity profile of the combination is tolerable with manageable hematologic side effects. These results support the design of clinical trial with this chemo-free combination as first line treatment for INFLs, in particular for MZL. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Randomized Trial of Lenalidomide Alone Versus Lenalidomide Plus Rituximab in Patients With Recurrent Follicular Lymphoma: CALGB 50401 (Alliance)

2015 ◽  
Vol 33 (31) ◽  
pp. 3635-3640 ◽  
Author(s):  
John P. Leonard ◽  
Sin-Ho Jung ◽  
Jeffrey Johnson ◽  
Brandelyn N. Pitcher ◽  
Nancy L. Bartlett ◽  
...  
Keyword(s):  
Adverse Events ◽  
Follicular Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Dose Intensity ◽  
Complete Response ◽  
Time To Progression ◽  
Non Hodgkin Lymphoma ◽  
Grade 3 ◽  
Group B

Purpose Lenalidomide and rituximab (LR) are active agents in follicular lymphoma (FL). Combination regimens have not been previously assessed in randomized studies. Patients and Methods The Cancer and Leukemia Group B (Alliance) 50401 trial is a randomized phase II trial studying rituximab (375 mg/m2 weekly for 4 weeks), lenalidomide (15 mg per day on days 1 to 21, followed by 7 days of rest, in cycle 1 and then 20 mg per day on days 1 to 21, followed by 7 days of rest, in cycles 2 to 12), or LR. The rituximab-alone arm was discontinued as a result of poor accrual. Eligibility included recurrent FL and prior rituximab with time to progression of ≥ 6 months from last dose. Aspirin or heparin was recommended for patients at high thrombosis risk. Results Ninety-one patients (lenalidomide, n = 45; LR, n = 46) received treatment; median age was 63 years (range, 34 to 89 years), and 58% were intermediate or high risk according to the Follicular Lymphoma International Prognostic Index. In the lenalidomide and LR arms, grade 3 to 4 adverse events occurred in 58% and 53% of patients, with 9% and 11% of patients experiencing grade 4 toxicity, respectively; grade 3 to 4 adverse events included neutropenia (16% v 20%, respectively), fatigue (9% v 13%, respectively), and thrombosis (16% [n = 7] v 4% [n = 2], respectively; P = .157). Thirty-six percent of lenalidomide patients and 63% of LR patients completed 12 cycles. Lenalidomide alone was associated with more treatment failures, with 22% of patients discontinuing treatment as a result of adverse events. Dose-intensity exceeded 80% in both arms. Overall response rate was 53% (20% complete response) and 76% (39% complete response) for lenalidomide alone and LR, respectively (P = .029). At the median follow-up of 2.5 years, median time to progression was 1.1 year for lenalidomide alone and 2 years for LR (P = .0023). Conclusion LR is more active than lenalidomide alone in recurrent FL with similar toxicity, warranting further study in B-cell non-Hodgkin lymphoma as a platform for addition of novel agents.

First-MIND: A phase Ib, open-label, randomized study to assess safety of tafasitamab (tafa) or tafa + lenalidomide (LEN) in addition to R-CHOP in patients with newly diagnosed DLBCL.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7540-7540
Author(s):  
David Belada ◽  
Katerina Kopeckova ◽  
Juan Miguel Bergua ◽  
Marc André ◽  
Ernesto Perez Persona ◽  
...  
Keyword(s):  
Performance Status ◽  
Randomized Study ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Dose Intensity ◽  
Newly Diagnosed ◽  
Open Label ◽  
Bulky Disease ◽  
Phase Ib ◽  
Ecog Ps

7540 Background: Tafasitamab is a humanized, Fc-modified anti-CD19 monoclonal antibody that enhances antibody-dependent cellular cytotoxicity and phagocytosis. It is FDA-approved with LEN for adult patients (pts) with relapsed/refractory (R/R) DLBCL ineligible for autologous stem cell transplantation. First-MIND (NCT04134936) is a Phase Ib, open-label, randomized study of tafa + R-CHOP or tafa + LEN + R-CHOP in newly diagnosed DLBCL. Methods: Eligible pts were ≥18 years, treatment-naïve, with histologically confirmed DLBCL not otherwise specified, international prognostic index (IPI) 2–5 and ECOG performance status (PS) 0–2. Pts with known double- or triple-hit and transformed lymphoma were excluded. Treatment (Tx) comprised six 21-day cycles of tafa (12 mg/kg IV, Day [D] 1, 8, 15) + R-CHOP (arm A) or tafa (12 mg/kg IV, D1, 8, 15) + LEN (25 mg orally, D1–10) + R-CHOP (arm B). G-CSF and VTE prophylaxis was mandatory. Primary objective is safety; secondary objectives are ORR, PET-CR rate at end of Tx, PFS, long-term safety, pharmacokinetics, immunogenicity. Results: From Dec 2019 to Aug 2020, 83 pts were screened in Europe and the US; 66 were randomized (33 per arm). Data cut-off for this analysis: 9 Dec 2020; study is ongoing. Median age was 64.5 years (range 20–86). Overall, 30% (20/66) of pts were ≥70 years and many had high-risk disease: IPI 2 29%, IPI 3 46%, IPI 4 26%. ECOG PS: 47% of pts were ECOG PS 0, 44% PS 1, 9% PS 2. Most pts had stage III/IV disease (92%); 46% had bulky disease. All pts experienced a treatment-emergent adverse event (TEAE). Grade ≥3 neutropenia and thrombocytopenia occurred in 54.5% and 12.1% (arm A) and 66.7% and 30.3% (arm B) of pts, respectively (Table). Serious TEAEs occurred in 42.4% (arm A) and 51.5% (arm B) of pts. There were three deaths, unrelated to tafa and/or LEN (sepsis, urosepsis, and COVID-19 pneumonia). R-CHOP dose intensity was maintained in both arms. Among 60 pts who completed tumor assessments after cycle 3, ORR was 89.7% (arm A) and 93.5% (arm B). Conclusions: These data suggest R-CHOP + tafa or tafa + LEN is tolerable in pts with Tx-naïve DLBCL and that R-CHOP dosing is not affected. Toxicities are similar to those expected with R-CHOP or R-CHOP + LEN. Updated safety and early efficacy data will be presented at the conference. Clinical trial information: NCT04134936. [Table: see text]

Phase II Study of Uracil-Tegafur With Leucovorin in Elderly (≥ 75 years old) Patients With Colorectal Cancer: ECOG 1299

2007 ◽  
Vol 25 (34) ◽  
pp. 5397-5402 ◽  
Author(s):  
Howard S. Hochster ◽  
Weixiu Luo ◽  
Elizabeta C. Popa ◽  
Bruce T. Lyman ◽  
Mary Mulcahy ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Elderly Patients ◽  
Survival Time ◽  
Phase Ii ◽  
Performance Status ◽  
Progression Free Survival ◽  
Open Label ◽  
Old Patients ◽  
Gi Toxicity ◽  
Grade 3

Purpose To evaluate the tolerability and effectiveness of uracil-tegafur (UFT) with leucovorin (LV) in the treatment of elderly patients with advanced colorectal cancer. Patients and Methods Patients ≥ 75 years of age with previously untreated colorectal cancer were eligible for this phase II, single-arm, open-label, multicenter cooperative group clinical trial. UFT 100 mg/m2 plus LV 30 mg orally every 8 hours for 28 days every 35 days was administered until progression. Results Fifty-eight patients were enrolled between June 2000 and July 2001, and 55 were treated. The median age of treated patients was 81 years (range, 75 to 90 years), 26 patients were (47%) women, and 80% had good performance status (0 to 1). The observed overall response rate was 22% (95% CI, 11.8% to 35.0%). The estimated median overall survival time was 13.0 months (95% CI, 9.6 to 17.4 months), and median progression-free survival time was 4.6 months (95% CI, 2.6 to 6.7 months). Among the 56 treated patients (including one ineligible patient), 31 (55%) experienced grade 3 to 4 toxicities, most commonly diarrhea (25%) and GI toxicity (36%), with patients older than 85 years of age at highest risk. Conclusion The results of this trial support the efficacy of oral UFT/LV in elderly patients with colorectal cancer. The regimen is tolerated moderately well overall, particularly as compared with other fluoropyrimidine regimens, although there is increased GI toxicity in the most elderly. These results suggest that studies using newer oral fluoropyrimidine analogs should be investigated in this patient population.

Cisplatin and Gemcitabine Treatment for Malignant Mesothelioma: A Phase II Study

1999 ◽  
Vol 17 (1) ◽  
pp. 25-25 ◽  
Author(s):  
M. J. Byrne ◽  
J. A. Davidson ◽  
A. W. Musk ◽  
J. Dewar ◽  
G. van Hazel ◽  
...  
Keyword(s):  
Partial Response ◽  
Phase Ii ◽  
Malignant Mesothelioma ◽  
Phase Ii Study ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Complete Response ◽  
Symptom Improvement ◽  
Median Response ◽  
Grade 3

PURPOSE: We performed a phase II study of combined cisplatin 100 mg/m2, given intravenously on day 1, and gemcitabine 1,000 mg/m2, given intravenously on days 1, 8, and 15 of a 28-day cycle for six cycles among patients with advanced measurable pleural mesothelioma. PATIENTS AND METHODS: Pleural tumor was measured at three levels on computed tomographic scans at study entry and before the second, fourth, and sixth cycles and every 2 months thereafter to disease progression. Of the 21 patients treated, 19 were male; the median age was 62 years (range, 46 to 74 years); 62% had epithelial tumors; and 18 were classified as tumor-node-metastasis system stage III or IV. Ninety-four cycles were given (median, six; mean, 4.5 per patient), with a mean relative dose intensity of cisplatin 96.7% and gemcitabine 82.5%. RESULTS: Best objective responses achieved were as follows: complete response, no patients; partial response, 10 patients (complete response + partial response, 47.6% [95% confidence interval, 26.2% to 69.0%]); no change, nine patients; and progressive disease, two patients. Median response duration was 25 weeks, progression-free survival was 25 weeks, and overall survival was 41 weeks. Nine of the 10 responders (90%) and three of nine patients with no change had significant symptom improvement. Serial measurements of vital capacity were performed on three of the responders; all showed a significant increase during the time of remission. Toxicity was mainly gastroenterologic and hematologic. Grade 3 nausea and vomiting occurred in 33% of patients, grade 3 leukopenia in 38%, grade 3 thrombocytopenia in 14%, and grade 4 thrombocytopenia in 19%. CONCLUSION: Combined cisplatin and gemcitabine is an active combination in malignant mesothelioma and produces symptomatic benefit in responding patients.

scholarly journals Short regimen of rituximab plus lenalidomide in follicular lymphoma patients in need of first-line therapy

Blood ◽  
2019 ◽  
Vol 134 (4) ◽  
pp. 353-362 ◽  
Author(s):  
Emanuele Zucca ◽  
Stephanie Rondeau ◽  
Anna Vanazzi ◽  
Bjørn Østenstad ◽  
Ulrich J. M. Mey ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Progression Free Survival ◽  
Complete Response ◽  
Clinical Cancer Research ◽  
International Prognostic Index Score ◽  
First Line Therapy ◽  
Phase 2 Trial ◽  
Grade 3

Abstract The SAKK 35/10 phase 2 trial, developed by the Swiss Group for Clinical Cancer Research and the Nordic Lymphoma Group, compared the activity of rituximab vs rituximab plus lenalidomide in untreated follicular lymphoma patients in need of systemic therapy. Patients were randomized to rituximab (375 mg/m2 IV on day 1 of weeks 1-4 and repeated during weeks 12-15 in responding patients) or rituximab (same schedule) in combination with lenalidomide (15 mg orally daily for 18 weeks). Primary end point was complete response (CR)/unconfirmed CR (CRu) rate at 6 months. In total, 77 patients were allocated to rituximab monotherapy and 77 to the combination (47% poor-risk Follicular Lymphoma International Prognostic Index score in each arm). A significantly higher CR/CRu rate at 6 months was documented in the combination arm by the investigators (36%; 95% confidence interval [CI], 26%-48% vs 25%; 95% CI, 16%-36%) and confirmed by an independent response review of computed tomography scans only (61%; 95% CI, 49%-72% vs 36%; 95% CI, 26%-48%). After a median follow-up of 4 years, significantly higher 30-month CR/CRu rates and longer progression-free survival (PFS) and time to next treatment (TTNT) were observed for the combination. Overall survival (OS) rates were similar in both arms (≥90%). Toxicity grade ≥3 was more common in the combination arm (56% vs 22% of patients), mainly represented by neutropenia (23% vs 7%). Addition of lenalidomide to rituximab significantly improved CR/CRu rates, PFS, and TTNT, with expected higher, but manageable toxicity. The excellent OS in both arms suggests that chemotherapy-free strategies should be further explored. This trial was registered at www.clinicaltrials.gov as #NCT01307605.

Polypharmacy and potentially inappropriate medication use in older patients with aggressive non-Hodgkin lymphoma (NHL) leads to inferior survival and increased treatment-related toxicities.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 10039-10039 ◽  
Author(s):  
Richard Jirui Lin ◽  
Helen Ma ◽  
Robin Guo ◽  
Michael L. Grossbard ◽  
Andrea B. Troxel ◽  
...  
Keyword(s):  
Older Patients ◽  
Inappropriate Medication ◽  
International Prognostic Index ◽  
Tumor Biology ◽  
Prognostic Index ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Rank Test ◽  
Potentially Inappropriate Medications ◽  
Grade 3

10039 Background: Survival outcomes for older patients with aggressive NHL are disproportionally inferior to those of younger patients. While differences in tumor biology may play a role, older patients are often frail with comorbidities, polypharmacy, and use potentially inappropriate medications (PIM) such as anticholinergics and benzodiazepines. Methods: Using Cox proportional hazard and logistic regression models, we analyzed all aggressive NHL patients age ≥60 treated at our two affiliated hospitals from 2009-2014 to examine the association of polypharmacy and PIM use with progression-free survival (PFS), overall survival (OS), and treatment-related toxicities. Results: In this updated and final analysis, we included 171 patients with complete records from these two hospitals. They share similar demographic, clinical, and laboratory characteristics except for higher International Prognostic Index (IPI) in patients from one hospital. The median age was 70 years (range 65-77). At the time of diagnosis, 46% of patients used more than 4 medications (polypharmacy) and 47% used at least one PIM. Only 43% of patients received first-line chemotherapy of adequate relative dose intensity (>85% dosage), and 65% experienced ≥grade 3 toxicities. Polypharmacy and PIM use were associated with shortened PFS and OS by log-rank test. Most importantly, PIM use remained an independent predictor of PFS, OS, and ≥ grade 3 toxicities in multivariable analyses (Table). Conclusions: This is the first report of significantly adverse survival impacts of polypharmacy and PIM use in older patients with aggressive NHL, presumably from drug-drug interactions that increase toxicities and impair the delivery of adequate chemotherapy dosage. Our findings support the use of evidence-based geriatric principles to guide meticulous medication management to improve outcome disparity for these patients. [Table: see text]

scholarly journals PDCT-05. FINAL RESULTS OF THE VINILO OPEN-LABEL PHASE II RANDOMIZED TRIAL FOR PEDIATRIC LOW-GRADE GLIOMAS (pLGG) COMPARING THE COMBINATION VINBLASTINE-NILOTINIB WITH VINBLASTINE ALONE

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi184-vi184
Author(s):  
Jacques Grill ◽  
Caroline Brard ◽  
Sue Picton ◽  
Ofelia Cruz ◽  
A Y N Schouten-vanMetteren ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase Ii ◽  
Single Agent ◽  
Dose Intensity ◽  
Initial Therapy ◽  
Optic Pathway Glioma ◽  
Low Grade ◽  
Open Label ◽  
Intention To Treat ◽  
Grade 3

Abstract Chemotherapy is the mainstay of non-surgical treatment in pLGG but many patients progress again after the end of the first treatment. Apart from the standard carboplatin-vincristine, new regimens with less toxicity are therefore desirable. Single agent vinblastine is an established regimen. PDGFRA TKI inhibitors have shown efficacy in refractory pLGG as well. The VINILO phase I showed the feasibility of the combination of vinblastine with nilotinib at the expense of a 50% decrease of the dose of vinblastine. The phase II trial therefore compared vinblastine 6 mg/m2 weekly (standard arm) to vinblastine 3mg/m2 weekly plus nilotinib 230mg/m2/day. The primary endpoint was the PFS, analysed on the intention-to-treat population. The target sample size was 120 patients. Accrual was stopped after recruitment of 109 patients (53 and 56 in the vinblastine-arm and the vinblastine+nilotinib arm, respectively) between July 2016 and April 2019. Fifty-four patients had an optic pathway glioma and 45 had NF1 (these patients were allowed to enter the trial as initial therapy). Half of the patients were treated after more than one line of therapy. The planned interim analysis showed that the vinblastine+nilotinib arm was associated with a worse PFS as compared to the standard arm (HR=2.37; 95%CI, 1.26–4.46; p=0.007; with 2-year PFS of 28% versus 49%). Overall, 156 biological adverse events (AE) of grade ≥ 3 have been reported after randomization (94 in vinblastine alone arm, 62 in vinblastine+nilotinib arm) and 84 non-biological adverse events of grade ≥ 3 (50 in vinblastine alone arm, 34 in vinblastine+nilotinib arm). We conclude that the combination of vinblastine plus nilotinib was less effective than vinblastine alone, possibly because of a lower dose intensity of vinblastine in the experimental arm. Vinblastine can serve as a backbone for combinations but lowering its dose may jeopardize the efficacy.

XELOX with bevacizumab in elderly patients age 75 or older with metastatic colorectal cancer: Results of a planned interim analysis for multicenter phase II ASCA study.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 502-502 ◽  
Author(s):  
Keiichiro Ishibashi ◽  
Yoshinori Munemoto ◽  
Masaki Matsuoka ◽  
Taishi Hata ◽  
Michiya Kobayashi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Renal Function ◽  
Elderly Patients ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Performance Status ◽  
Primary Objective ◽  
Open Label ◽  
Ecog Performance Status ◽  
Grade 3

502 Background: Combination chemotherapy of capecitabine plus oxaliplatin (XELOX) with bevacizumab is commonly used as standard chemotherapy for metastatic colorectal cancer (mCRC). A previous meta-analysis showed that there was no difference between two age groups of <65 years and ≥65 years on overall survival (OS) after treatment with chemotherapy with bevacizumab. However, the safety and efficacy of XELOX with bevacizumab in elderly patients (pts) ≥75 years with mCRC remain unclear. Methods: This study was an open-label multicentre phase II study to evaluate the efficacy and safety of XELOX with bevacizumab in pts ≥75 years with metastatic CRC. The primary objective was to assess progression-free survival (PFS). The secondary endpoints were the safety, response rate (RR), time to treatment-failure (TTF) and OS. Results: 36 pts were enrolled. Pts characteristics were; median age 78 (range 75-86); male/female, 21/15; ECOG performance status 0/1, 30/6; colon/rectum 24/12, creatinine clearance (CCr) 60.2 ml/min (range 32.6-84.6). Median follow-up period was 220 days. RR was 55.6% and median TTF was 209 days. The median PFS and median OS are not reached. Grade 3 or 4 adverse events (AEs) were reported in 22 pts (62.8%). Common grade 3 or 4 AEs were hypertension (11.4%), leukopenia (20.0%), peripheral sensory neuropathy (14.3%), hand foot syndrome (8.6%), and fatigue (8.6%). Examining the relationship between renal function (CCr) and AEs, the incidence of Grade 3 or 4 AEs in the lower CCr group was significantly higher than that in the higher CCr group (61.6% vs. 47.8%; p=0.013); hematological toxicities (87.5% vs. 14.8%; p=0.0003) and non-hematological toxicities (61.5% vs. 11.1%; p=0.018). Conclusions: XELOX with bevacizumab is safely administered in elderly patients ≥75 years. Renal function (CCr) could be a good predictive marker for grade 3 or 4 AEs. Clinical trial information: UMIN000003500.

Anlotinib and irinotecan for advanced Ewing sarcoma after failure of standard therapy: A multicenter, two-cohort, single-arm, open label, phase Ib/II trial (NCT03416517).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 11012-11012
Author(s):  
Jie Xu ◽  
Lu Xie ◽  
Wei Guo ◽  
Xiaodong Tang ◽  
Rongli Yang ◽  
...  
Keyword(s):  
Phase Ii ◽  
Ewing Sarcoma ◽  
Initial Level ◽  
Objective Response ◽  
Complete Response ◽  
Fixed Dose ◽  
Open Label ◽  
Phase Ib ◽  
Open Label Phase ◽  
Grade 3

11012 Background: Both protracted irinotecan and anti-angiogenesis therapy have shown promising results in Ewing sarcoma. We did this phase Ib/II trial to first define the proper dose of irinotecan in combination with anlotinib in Ewing sarcoma and then evaluate efficacy. Methods: Patients diagnosed with recurrent or refractory Ewing sarcoma were enrolled and sub-classified into cohort A (≥16y) or cohort B ( < 16y). In the dose-defining phase Ib portion, anlotinib was given at a fixed dose of 12mg D1-14every 21 days, while the de-escalated 3+3 design was used to detect the recommended dose of irinotecan in each cohort from an initial level of 20mg/m2/d dx5x2. Recommended phase 2 dose (RP2D) was defined as the highest dose at which no more than 30% patients experience a DLT in the first two courses. In the next dose-expanding phase II portion, the primary endpoint was objective response rate at 12 weeks (ORR12w). A conventional two-stage study design model was used. Results: 41 patients were enrolled with 29 in cohort A and 12 in cohort B. For cohort A, first 5 patients were treated at initial level in phase Ib portion, two of whom subsequently experienced delayed diarrhea as dose-limiting toxicity (DLT). Additional six patients were then treated at a lower dose of 15mg/m2. Since no more DLT was recorded, it was used as RP2D. 23/24 patients in cohort A phase II were available for response evaluation at 12 weeks, with one complete response (CR), 14 partial response (PR) (including one CMR who has a negative PET/CT scan but still abnormal lesions in MR scan), 2 stable disease (SD) and 6 progressive disease (PD). ORR12wwas 62.5%. For cohort B, no DLT was noticed in the first six patients treated at the initial level which was used as RP2D later. Finally, 12 patients were included in cohort B. ORR12wwas 83.3% with two CR, 8 PR (including one CMR) and two PD. Although effective, cohort B were closed because of slow enrollment. Most common grade 3/4 adverse events were diarrhea, abdominal pain and neutropenia. The genotype of UGT1A1*1 and UGT1A1*28 were not associated with the risk of diarrhea. Conclusions: The combination of irinotecan and anlotinib demonstrated an acceptable toxicity profile with promising evidence of clinical efficacy in advanced Ewing sarcoma. Clinical trial information: NCT03416517.

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