Bendamustine In Combination With Rituximab As First-Line Treatment For Indolent Non-Hodgkin Lymphoma: Retrospective Analysis Of An Spanish Registry

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5094-5094 ◽  
Author(s):  
Silvia Solorzano ◽  
Carmen Martinez-Chamorro ◽  
Carlos Panizo ◽  
Cristina Quero ◽  
Guillermo Deben ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Bone Marrow Involvement ◽  
Common Adverse Event ◽  
Hematological Toxicity ◽  
Line Treatment ◽  
Compassionate Use ◽  
First Line ◽  
Bulky Disease ◽  
Grade 3 ◽  
First Line Treatment

Abstract Introduction Indolent lymphomas represent 40% of all subtypes of non-Hodking's lymphoma, of which follicular lymphoma (FL) is the most frequent. Bendamustine is a dual alkylating agent with demonstrated high efficacy and low toxicity profile in reported clinical trials. We present the preliminary results from the experience of Spanish compassionate use registry of this agent as first-line treatment for indolent lymphoma. Methods Retrospective multicenter analysis of patients with indolent non-Hodgkin lymphomas (iNHL) treated as frontline with Bendamustine plus Rituximab (BR) in compassionate use. Clinical efficacy was evaluated according to Cheson criteria (2007) and toxicity according to CTCAE v3.0 scale. This study has been approved by local ethical committees. Results Patients’ characteristics: There are 96 patients registered (9 centers), with the following diagnoses: FL: 62 (64.5%), marginal zone 24 (25%), Waldenström macroglobulinemia 7 (7.3%) and mantle NHL 3 (3.1%). The main clinical features of the series are: 45% males, median age 64 years (range 36-84), 87.1% ECOG≤ 1, 63% Ann Arbor stage IV, 50.5% high risk FLIPI and 43.7% CIRS ≥ 4. Extranodal involvement was present in 79.1% of the patients, bone marrow  involvement in 52% and 11 patients (11.9%) had bulky disease. Treatment consisted in 6 cycles of BR (B-90 mg/m2 D1-2, R-375mg/m2 D1) in 95% patients. Median number of cycles administrated was 6 (range 1-8). G-CSF support was administered in 16.1% of cycles. Response and Safety: Overall response rate was 95%, with 65.5 % CR, 13.1% uCR and 16.4% PR in the 61 evaluable patients. Progression was documented in 4.9% of patients. Three exitus ocurred due to aspergillosis, progression and other not related with LNH. Median follow-up period was 14 months (3-47). In general, treatment was well tolerated; over 461 cycles registered, the most common adverse event was hematological toxicity with grade 3-4 neutropenia in 10.4%, grade 3-4 leucocitopenia in 6.9% and grade 3-4 anemia in 1.9% of the cycles. Other toxicities included all grades infections in 3.2% of patients, gastrointestinal in 3.4%, asthenia in 3.2%, chills in 1.1%, and mucositis 0.4%. Only 9 hospitalizations due to febrile neutropenia were reported. Conclusion Bendamustine plus rituximab was an effective and well tolerated regimen for newly diagnosed patients with indolent NHL. Disclosures: No relevant conflicts of interest to declare.

Prolonged gemcitabine infusion as radiosensitizer for newly diagnosed glioblastoma multiforme (GBM): A phase I study

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 1581-1581
Author(s):  
C. M. Carapella ◽  
A. M. Mirri ◽  
A. Felici ◽  
A. Vidiri ◽  
A. Pace ◽  
...  
Keyword(s):  
Combined Treatment ◽  
Malignant Gliomas ◽  
Fixed Dose ◽  
Hematological Toxicity ◽  
Line Treatment ◽  
First Line ◽  
Total Period ◽  
Level 1 ◽  
Grade 3 ◽  
First Line Treatment

1581 Background: The use of cytotoxic drugs concurrent with RT represents a promising approach in the combined treatment of malignant gliomas. Gemcitabine (dFdCyd) is a drug widely explored for its potential radiomimetic activity in different tumors. The present study was aimed to evaluate the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of weekly prolonged dFdCyd infusion, administered in combination with RT as first line treatment, in adult pts affected by supratentorial GBM. Methods: Within 6 weeks after surgery, in the presence of measurable residual disease and KPS >70, pts were treated with fractionated RT at a dose of 2.0 Gy/daily fractions, 5 days a week (global dose 60 Gy). From 24 to 72 hours before the first RT application, and afterwards once weekly, pts received concurrent dFdCyd, at fixed dose rate of 10 mg/m2/min, over a total period of six weeks. Planned dose levels of dFdCyd started from 200 mg/m2/weekly (level 1), with sequential steps of 25 mg/m2/w based on toxicity. Results: Ten pts were enrolled into the study: six were male, median age 55.2 years (range 44–75), with a median KPS at baseline of 85 (SD 9.71). The median time from diagnosis to the start of treatment was six weeks (range 4–7). The median RT duration was 6 weeks (range 4–7), all but one pt received the planned dose and all pts received concomitant CT. Four pts entered at Level 1; one pt was excluded from the study, due to rapid progressive disease during the treatment. Two of the three valuable pts presented a relevant neurological worsening; on this basis the dFdCyd dose was reduced to 175 mg/m2/w (Level -1). A total of six pts were entered at Level -1, and none of them reported DLT. No hematological grade 3–4 toxicity was reported. Grade 3 non-hematological toxicity was observed in one pt (transaminases increase). After a median follow-up of 13.4 months (range 3–24), the median progression-free survival was 8 months (CI 95% 1–18), and the median overall survival was 14 months (CI 95% 12–17). Conclusions: The recommended dose of prolonged infusion of dFdCyd concomitant with RT is 175 mg/m2/w. The observed activity has been considered interesting enough to support a phase II study of this concurrent CT-RT schedule as first line treatment in GBM. [Table: see text]

OS05.7.A Absence of severe hematological toxicity during first line treatment predicts low chance on severe toxicity during second line alkylating chemotherapy in glioblastoma

2021 ◽  
Vol 23 (Supplement_2) ◽  
pp. ii8-ii8
Author(s):  
F E L van den Elzen ◽  
N Grun ◽  
J Osinga ◽  
A N van der Vegt ◽  
L de Glopper ◽  
...  
Keyword(s):  
Hematological Toxicity ◽  
Severe Thrombocytopenia ◽  
Severe Toxicity ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Infiltrative Growth Pattern ◽  
Grade 3 ◽  
Line Chemotherapy ◽  
First Line Treatment

Abstract BACKGROUND Glioblastoma has an infiltrative growth pattern that makes complete resection of the tumor virtually impossible. Sooner or later the tumor progresses, even after aggressive treatment with maximal safe resection, radiotherapy and/or chemotherapy. Hematological toxicity is an important cause of treatment delays during 1st line treatment. How often hematological toxicity occurs during 2nd line treatment is unclear. We explored rates of hematological toxicities in patients treated with temozolomide or lomustine at progression and investigated the association between severe toxicity during 1st and 2nd line treatment. METHODS We studied a retrospective cohort study of adult patients (n=247) with a glioblastoma treated with 2nd line alkylating chemotherapy at the Brain Tumor Center Amsterdam between 2000 and 2020. First line treatment of these patients consisted of a combination of radiotherapy combined with different treatments (80% received temozolomide, 4% PCV, 6% other chemotherapy and 10% radiotherapy only). Second line treatment consisted of temozolomide or lomustine. Mild and severe hematological toxicity were defined according to the CTCAE (version 5.0) criteria as a grade 1&2 and grade ≥3, respectively. We used descriptive statistics to analyze frequencies of hematological toxicity in patients with glioblastoma treated with 2nd line chemotherapy. RESULTS Sixty percent (147/247) of patients treated with 2nd line chemotherapy experienced hematological toxicity (grade 1–4). Considering subtypes of hematological toxicities, more patients experienced hematological toxicity during 2nd line treatment; severe thrombocytopenia occurred most frequently observed (6,1 during 1st line vs. 10,5% during 2nd line treatment), followed by neutropenia (3,6 vs. 6,9%), leukocytopenia (4,0 vs. 5,3%) and anemia (0 vs. 0,8%). Fewer patients treated with 2nd line temozolomide (n=113) experienced mild and severe hematological toxicity than patients treated with 2nd line lomustine (n=134; 46% versus 71% (for mild) and 12% vs 21% (severe toxicity), respectively). A subset of 107 patients was initially treated with radiotherapy and concurrent and adjuvant temozolomide; within this subset, patients with none or only mild toxicity during 1st line treatment had only a small risk of severe hematological toxicity during 2nd line treatment (4%). In contrast, the 34,5 % of patients with severe hematological toxicity during 1st line treatment also experienced severe hematological toxicity during 2nd line alkylating chemotherapy. CONCLUSION Hematological toxicity occurs more frequently during 2nd line treatment. Treatment with 2nd line temozolomide results in less hematological toxicity than lomustine. Absence of severe toxicity during 1st line treatment is predictive for the risk of toxicity during 2nd line treatment.

Phase IIb trial of fluorouracil, leucovorin, oxaliplatin, and paclitaxel (POF) compared with fluorouracil, feucovorin, and irinotecan (IF) as first-line treatment for advanced gastric cancer (AGC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15642-e15642
Author(s):  
R. Lin ◽  
Q. Chen ◽  
N. Fan ◽  
Y. Ye ◽  
Z. Guo ◽  
...  
Keyword(s):  
Gastroesophageal Junction ◽  
Complete Response ◽  
Patient Choice ◽  
Hematological Toxicity ◽  
Line Treatment ◽  
First Line ◽  
Peripheral Neurotoxicity ◽  
Grade 3 ◽  
First Line Treatment

e15642 Background: Primary results of POF as 1st and 2nd line treatment for AGC have been presented at ASCO 2007 and 2008. We report here data on the feasibility and the toxicity of POF versus IF(Dank, et al, ASCO 2005) in 1st line treatment of AGC. Methods: Patients with previously untreated, advanced, unresectable, and histologically confirmed adenocarcinoma of the gastric or gastroesophageal junction were randomly assigned to POF or IF regiment. Treatment was continued until disease progressed, unacceptable toxicity, or patient choice. Results: 25 patients were entered in this study between March 2007 and July 2007: 13 in the POF group and 12 in the IF group. The median patient age was 55 years (range, 36 to 67 years), 18 were males and 7 were females. No complete response was observed. The response rate was 62.5% (POF) and 33.3% (IF) respectively. At a median follow-up of 285 days, 7(POF) versus 6(IF) patients were still alive. Hematological toxicity was the most frequent toxicity in both groups. Grade 3 to 4 neutropenia were 38.5% (POF) versus 8.3% (IF). Diarrhea was found 0% and 8.3% in POF and IF group respectively. No grade 3 peripheral neurotoxicity was observed. Conclusions: Compared with IF regiment, POF could also be used as first-line treatment for AGC with acceptable safety profile, good efficacy, and more encouraging results. No significant financial relationships to disclose.

Phase III Multicenter Randomized Trial of Oxaliplatin Added to Chronomodulated Fluorouracil–Leucovorin as First-Line Treatment of Metastatic Colorectal Cancer

2000 ◽  
Vol 18 (1) ◽  
pp. 136-136 ◽  
Author(s):  
S. Giacchetti ◽  
B. Perpoint ◽  
R. Zidani ◽  
N. Le Bail ◽  
R. Faggiuolo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Objective Response ◽  
Sensory Neuropathy ◽  
Phase Iii ◽  
Line Treatment ◽  
Survival Times ◽  
First Line ◽  
Grade 3 ◽  
First Line Treatment

PURPOSE: To study how adding oxaliplatin (l-OHP) to chronomodulated fluorouracil (5-FU)–leucovorin (LV) affected the objective response rate, as first-line treatment of metastatic colorectal cancer. PATIENTS AND METHODS: Two hundred patients from 15 institutions in four countries were randomly assigned to receive a 5-day course of chronomodulated 5-FU and LV (700 and 300 mg/m2/d, respectively; peak delivery rate at 0400 hours) with or without l-OHP on the first day of each course (125 mg/m2, as a 6-hour infusion). Each course was repeated every 21 days. Response was assessed by extramural review of computed tomography scans. RESULTS: Grade 3 to 4 toxicity from 5-FU–LV occurred in ≤ 5% of the patients (≤ 1% of the courses). Grade 3 to 4 diarrhea occurred in 43% of the patients given l-OHP (10% of the courses), and less than 2% of the patients had severe hematotoxicity. Thirteen percent of the patients had moderate functional impairment from peripheral sensory neuropathy. Sixteen percent of the patients receiving 5-FU–LV had an objective response (95% confidence interval [CI], 9% to 24%), compared with 53% of those receiving additional l-OHP (95% CI, 42% to 63%) (P < .001). The median progression-free survival time was 6.1 months with 5-FU–LV (range, 4.1 to 7.4 months) and 8.7 months (7.4 to 9.2 months) with l-OHP and 5-FU–LV (P = .048). Median survival times were 19.9 and 19.4 months, respectively. CONCLUSION: By chronomodulating 5-FU–LV, we were able to add l-OHP without compromising dose-intensities. l-OHP significantly improved the antitumor efficacy of this regimen.

JUPITER-02: Randomized, double-blind, phase III study of toripalimab or placebo plus gemcitabine and cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (NPC).

2021 ◽  
Vol 39 (18_suppl) ◽  
pp. LBA2-LBA2
Author(s):  
Rui-hua Xu ◽  
Hai-Qiang Mai ◽  
Qiu-Yan Chen ◽  
Dongping Chen ◽  
Chaosu Hu ◽  
...  
Keyword(s):  
Interim Analysis ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Phase Iii ◽  
Line Treatment ◽  
First Line ◽  
Double Blind ◽  
Grade 3 ◽  
First Line Treatment

LBA2 Background: Gemcitabine-cisplatin (GP) chemotherapy is the standard 1st line treatment for locally advanced, recurrent or metastatic (r/m) NPC. Toripalimab, a humanized IgG4K monoclonal antibody specific for PD-1, provided durable responses in patients (pts) with r/m NPC as monotherapy in the ≥2nd line setting (POLARIS-02 study). The results of JUPITER-02, a randomized, placebo-controlled, double-blinded Phase III trial of toripalimab in combination with GP chemotherapy as first-line treatment for r/m NPC are summarized. Methods: Pts with advanced NPC with no prior chemotherapy in the r/m setting were randomized (1:1) to receive toripalimab 240 mg or placebo d1 in combination with gemcitabine 1000 mg/m2 d1, d8 and cisplatin 80 mg/m2 d1 every 3 weeks (Q3W) for up to 6 cycles, followed by monotherapy with toripalimab or placebo Q3W until disease progression, intolerable toxicity, or completion of 2 years of treatment. Stratification factors were ECOG PS (0 vs. 1) and extent of disease (recurrent vs. primary metastatic) at enrollment. Progression-free survival (PFS) and response were assessed by independent review committee (IRC) per RECIST v1.1. The primary endpoint was PFS by IRC in the ITT population. Secondary end points included ORR, DOR and OS. There was one prespecified interim analysis of PFS at 130 PFS events with a planned final analysis at 200 PFS events. Results: 289 pts were randomized: 146 to the toripalimab arm and 143 to the placebo arm. By May 30, 2020 as the interim analysis cutoff date, the median treatment duration was 39 weeks in the toripalimab arm and 36 weeks in the placebo arm. A significant improvement in PFS was detected for the toripalimab arm compared to the placebo arm (HR = 0.52 [95% CI: 0.36-0.74] two-sided p = 0.0003), with median PFS of 11.7 vs. 8.0 months. The 1-year PFS rates were 49% and 28% respectively. An improvement in PFS was observed across relevant subgroups, including all PD-L1 subgroups. The ORR was 77.4% vs. 66.4% (P = 0.033) and the median DOR was 10.0 vs. 5.7 months (HR = 0.50 [95% CI: 0.33-0.78]). As of Jan 15, 2021, OS was not mature, with 25 deaths in the toripalimab arm and 35 in the placebo arm (HR = 0.68 [95% CI: 0.41-1.14], P = 0.14). The incidence of Grade ≥3 adverse events (AEs) (89.0% vs 89.5%); AEs leading to discontinuation of toripalimab/placebo (7.5% vs 4.9%); and fatal AEs (2.7% vs 2.8%) were similar between two arms; however, immune-related (irAEs) (39.7% vs. 18.9%) and Grade ≥3 irAEs (7.5% vs. 0.7%) were more frequent in the toripalimab arm. Conclusions: The addition of toripalimab to GP chemotherapy as 1st-line treatment for pts with advanced NPC provided superior PFS and ORR and longer DOR than GP alone with a manageable safety profile. These results support the use of toripalimab with GP chemotherapy as the new standard care for this population. Clinical trial information: NCT03581786.

Comparative Safety Analysis of Currently Approved Anti-CD20 Monoclonal Antibodies for First Line Treatment of Chronic Lymphocytic Leukemia (CLL)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5587-5587
Author(s):  
Mkaya Mwamburi ◽  
Vasudha Bal ◽  
Teresa Cascella ◽  
Anshul Shah ◽  
Merena Nanavaty ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Safety Profile ◽  
Lymphocytic Leukemia ◽  
Line Treatment ◽  
Phase 2 ◽  
First Line ◽  
Grade 3 ◽  
Anti Cd20 ◽  
Cost Implications ◽  
First Line Treatment

Abstract Introduction: Treatment of CLL has advanced tremendously in the past decade with significant extension of life expectancy in patients diagnosed with the disease. Three anti-CD20 monoclonal antibody (mAB) combinations approved for previously untreated chronic lymphocytic leukemia (CLL) patients are obinutuzumab-chlorambucil (OBI-CHL), ofatumumab-chlorambucil (OFA-CHL), and rituximab-chlorambucil (RTX-CHL), have comparable efficacy but varying safety profiles in pivotal trials. Grade 3-4 adverse events (AEs), including infusion-related reactions (IRRs), neutropenia, thrombocytopenia, anemia, and infections differ by each mAB. Grade 3-4 AEs, defined as requiring hospitalization or life-threatening, result in reductions in patient quality of life (QoL) and bear cost implications. We sought to compare the safety of the IV-administered anti-CD20 mABs in the first-line treatment of CLL and to evaluate the respective QoL and economic implications of these AEs. Methods: A systematic literature review was conducted in PubMed, Embase, and Cochrane library for the time period of 2010-2016 and in conference proceedings of ASH, the American Society of Clinical Oncology (ASCO), and the European Hematology Association (EHA) for 2014-2016. Search was limited to clinical trials conducted on humans and published in English language. The IRRs were compared directly as CHL is administered orally. A Bayesian network meta-analyses (NMA) was conducted with data from phase 3 trials using SAS® (v9.3) to compare grade 3-4 neutropenia, thrombocytopenia, anemia, and infections associated with the three anti-CD20 mABs. A pooled analysis of data from phase 2 trials and cohort studies was conducted using MedCalc® version 16.2.1. Analyses were also conducted to estimate the potential impact of the AEs of respective anti-CD20 mABs on QoL and cost of care based on the NMA results and previously published estimates of utilities associated with CR (0.780), PR (0.790), SD/PD (0.760); disutilities associated with IRR (-0.11), neutropenia (-0.09), thrombocytopenia (-0.05), anemia (-0.09), and infections (-0.20); and costs associated with episodes of IRR ($4,482), neutropenia ($5,406), thrombocytopenia ($12,621), anemia ($8,894), and infections ($7,163) in CLL. Results: Of the 86 studies screened, 10 studies were included. Direct comparison showed that the rate of IRRs in OBI-CHL, OFA-CHL, and RTX-CHL were 21%, 10%, and 4%, respectively. Risks for neutropenia were lower for OFA-CHL compared to OBI-CHL (OR = 0.74; 95% CI: 0.12-4.59) and similar to RTX-CHL (1.08; 0.20-5.82); for thrombocytopenia were lower for OFA-CHL compared to OBI-CHL (0.16; 0.02-1.33) and to RTX-CHL (0.49; 0.06-4.15); for anemia were lower for OFA-CHL compared to OBI-CHL (0.80; 0.21-3.06) and similar to RTX-CHL (1.08; 0.24-4.64); and for infections OFA-CHL, OBI-CHL (1.00; 0.15-6.74) and RTX-CHL (0.86; 0.15-4.43) were similar. The pooled analyses of AEs observed in phase 2 / cohort studies revealed similar trends when assessed. The mean pre-progression QoL utilities associated with OBI-CHL, OFA-CHL, and RTX-CHL weighted by rates of AEs, utilities associated with respective response rates to treatments, and disutilities of the respective AEs were 0.772, 0.761, and 0.748 respectively. The total cost of treating AEs per 1,000 patients on OFA-CHL, OBI-CHL and RTX-CHL were $3.9M, $8.0M and $4.2M, respectively. Conclusion: The safety profile was most desirable for OFA-CHL, followed by RTX-CHL and OBI-CHL. Though RTX-CHL had the lowest rate of grade 3-4 IRR, OFA-CHL had the better grade 3-4 hematologic safety profile compared to OBI-CHL and RTX-CHL. As efficacy of CLL treatments has improved substantially, safety of treatments is increasingly important particularly on the impact of QoL. In addition, in the cost-conscious payer environment, selecting drugs with a better safety profile and lower cost implications is vital. Our findings demonstrate that better safety profile is associated with less impact on QoL and lower costs. We found that for every 1,000 patients covered by a payer, safety alone can save an excess of $4M based on regimen choice. Fewer incidences of AEs also results in better adherence and reduction in treatment interruption or discontinuation. Safety with the QoL and cost implications should be taken into consideration to maximize the overall benefits of the treatment to CLL patients. Disclosures Mwamburi: Novartis Pharmaceuticals: Consultancy. Bal:Novartis Pharmaceuticals: Employment. Cascella:Novartis Oncology: Employment. Shah:Novartis Pharmaceuticals: Consultancy. Nanavaty:Novartis Pharmaceuticals: Consultancy. Gala:Novartis Pharmaceuticals: Consultancy.

Tolerability of a weekly schedule of docetaxel-cisplatin as first-line treatment in patients with stage IIIB/IV non-small cell lung cancer (NSCLC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17112-17112
Author(s):  
D. Binder ◽  
M. Hackenthal ◽  
L. Graseck ◽  
H. Schweisfurth ◽  
C. Schäper ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Tumour Response ◽  
Low Frequency ◽  
Neutropenic Fever ◽  
Hematologic Toxicity ◽  
Weekly Schedule ◽  
Line Treatment ◽  
First Line ◽  
Grade 3 ◽  
First Line Treatment

17112 Background: Recent trials have shown that the combination docetaxel-cisplatin is an effective first-line treatment in locally advanced or metastatic NSCLC. However, the regimen can be associated with a marked rate of neutropenia. The present study tests the efficacy and tolerability of a weekly schedule of docetaxel and cisplatin. Methods: Patients (pts) with histologically confirmed NSCLC stages UICC IIIB (malignant effusion) or IV were treated with docetaxel (35 mg/m2, 30 min. infusion) and cisplatin (25 mg/m2, 30 min. infusion) on days 1, 8 and 15 repeated every 4 weeks for 4 to 6 cycles. This phase II study is scheduled to include 50 pts and primary endpoint is tumour response rate. Pts received 8 mg of ondansetron and 8 mg of dexamethasone i.v. preceding every day of therapy and oral dexamethasone 2 × 4 mg from the day before until the day after chemotherapy. NK1-antagonists were given at discretion of the investigator. In total, 2750 ml of volume were infused on each day of therapy. Most of the pts were treated in an outpatient department. Safety was assessed via common terminology criteria for adverse events v3.0 (CTCAE 3.0). Interim tolerability data is presented. Results: Currently, 28 pts were evaluable for this interim tolerability analysis. Pts received a median of 3 full cycles. There were no treatment-related deaths. Dose reductions of docetaxel and cisplatin due to poor tolerability were necessary in 3 pts (11%). No pts suffered from neutropenic fever while grade 3 neutropenia occurred in only 2 pts (7%). There was no grade 2/3/4 thrombocytopenia. 5 pts (18%) had grade 2 anemia, and 2 pts (7%) had an elevation of the plasma creatinine (both grade 1). Other toxicities were non-neutropenic infections (5/1/1 pts with grade 2, 3, 4, respectively), diarrhea (3 pts [11%] with grade 3), constipation (5 pts [18%] with grade 2) and mucositis (4 pts [14%] with grade 2/3). There was no grade 3/4 nausea or vomiting; 3 pts [11%] had grade 2 nausea/vomiting. Conclusions: In the present study, the combination of docetaxel and cisplatin appears well tolerated. It was associated with a very low frequency of severe hematologic toxicity or neutropenic fever. With relatively low hydration volumes it can be safely administered in an outpatient setting. [Table: see text]

Preliminary results from a phase II study of infusional 5-FU, leucovorin, and irinotecan (FOLFIRI) plus bevacizumab as first-line treatment for metastatic colorectal cancer (mCRC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3579-3579 ◽  
Author(s):  
S. Kopetz ◽  
J. L. Abbruzzese ◽  
C. Eng ◽  
R. B. Adinin ◽  
J. Morris ◽  
...  
Keyword(s):  
Phase Ii ◽  
Performance Status ◽  
Progression Free Survival ◽  
Line Treatment ◽  
First Line ◽  
Curative Surgery ◽  
Free Survival ◽  
Preliminary Results ◽  
Grade 3 ◽  
First Line Treatment

3579 Background: Irinotecan (I) plus bolus 5-FU (F) and leucovorin (L) comprise the IFL regimen, a very active treatment in mCRC when combined with bevacizumab (B). The response rate (RR) for IFL-B given as first-line treatment is 45%, with a median progression-free survival (PFS) of 10.6 months and a median survival of 20.3 months. The IFL regimen is now considered inferior to infusional 5-FU regimens, such as FOLFIRI, which have less toxicity and improved efficacy. Methods: We designed a 43 patient (pt), single-arm phase II trial of FOLFIRI-B with B (5mg/kg), I (180mg/m2), bolus of F (400mg/m2) and L (400mg/m2) followed by a 46-hour infusion of F (2400mg/m2), with a primary endpoint of progression-free survival (PFS). Chemotherapy naïve mCRC patients (pts) with adequate organ function and performance status 0–2 received B alone on Day minus 14, starting FOLFIRI + B on Day 1. DCE-MRI and laboratory correlates were completed before and after B alone and cycle 1. Once cycle is equivalent to two weeks. Results: 21 pts, median age 59 y/o (range 26–75), M:F = 15:6, 4 with prior F in adjuvant setting, have been enrolled to date. 20 pts are evaluable for response. One pt is too early. A total of 215 cycles have been administered (median 11). Median PFS has not been reached after a median follow-up of 8 months. By intent-to-treat analysis, there were 14 PRs (70%), and 5 (25%) pts with stable disease observed (including 1 unconfirmed PR). PRs were observed from 9 to 35 weeks after the first cycle (median: 18 weeks). 9 pts remain on treatment (1–12 months); 12 pts are off study (3 for progressive disease, 1 withdrew, 4 sent for curative surgery, 2 for toxicity, 2 sent for surgery unrelated to cancer). Toxicity included 10 cases of grade 3 neutropenia, including 1 febrile neutropenia, 4 venous thrombi, and 6 cases of hypertension requiring medication change. One pt included in the analysis developed peritonitis, considered a possible microperforation, after B alone and never received FOLFIRI. No ≥ grade 3 diarrhea was observed. Analysis of correlative studies will be presented at a later date. Conclusion: Our preliminary results indicate that FOLFIRI-B is well tolerated and an excellent choice as a first-line treatment for mCRC. [Table: see text]

Weekly versus 3-weekly docetaxel (D2) plus doxorubicin (D4) for first-line treatment of metastatic breast cancer (MBC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1101-1101
Author(s):  
H. Stemmler ◽  
N. Harbeck ◽  
I. Groell der Rivera ◽  
U. Vehling-Kaiser ◽  
G. Rauthe ◽  
...  
Keyword(s):  
Single Agent ◽  
Metastatic Breast ◽  
Hematological Toxicity ◽  
Weekly Schedule ◽  
First Line ◽  
Weekly Docetaxel ◽  
Grade 3 ◽  
To Receive ◽  
First Line Treatment ◽  
Weekly Application

1101 Background: We investigated the toxicity and efficacy of weekly applied docetaxel compared to its standard 3-weekly application in pts previously untreated with chemotherapy for MBC. Methods: In the D2 trial (>60 yrs or KPS 60–80%), pts were randomized to receive docetaxel either on a 3-weekly (75 mg/m2 q3w) or on a weekly schedule (30 mg/m2 d1, 8, 15 q4w). In the D4 study (<65 yrs or KPS 70–100%), pts received doxorubicin (50 mg/m2, d 1) in addition to docetaxel given either at q3w dose of 75 mg/m2 or at as 35 mg/m2 (days 1, 8, 15, q4w). Results: The primary endpoint (toxicity) was achieved in D2 and failed in D4. Both studies were terminated prematurely (D2 n = 102/162 D4 n = 85/242 pts). In the D2 study, leucopenia ≥grade 3 was significantly less frequent in the weekly arm (4.2% q1w versus 51.9% q3w, p < 0.0001). In the weekly versus 3-weekly arm ORR was 26.8% versus 46.9% (p = 0.08), TTP was 5.4 versus 6.3 months (p = 0.91), and OS was 22.7 versus 15.8 months (p = 0.24). In the D4 study, an unexpectedly low rate of leucopenia ≥grade 3 was observed in the 3-weekly arm (29.7% q3w versus 35.7% q1w, p = 0.21). In the weekly versus 3-weekly arm, ORR was 50.0% versus 55.0% (p = 0.82), TTP was 6.2 versus 10.3 months (p = 0.36), and OS was 20.5 versus 28.9 months (p = 0.98). Non-hematological toxicity ≥grade 3 was generally mild and comparable within the two schedules. Conclusions: The present data support the feasibility of both, the weekly and the 3-weekly regimen of docetaxel application either as a single-agent or in combination with doxorubicin. As expected, leucopenia seems avoidable in the weekly scheduled of single-agent docetaxel (D2), whereas a combined weekly schedule of docetaxel/doxorubicin as given in the D4 study failed to confirm an expected lower rate of leucopenia. [Table: see text]

Capecitabine and irinotecan (XELIRI) in first-line treatment of metastatic colorectal cancer (mCRC): A systematic review of controlled clinical trials

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15100-e15100
Author(s):  
S. Sukumaran ◽  
N. Pavlakis ◽  
K. B. Pittman ◽  
K. Patterson ◽  
T. J. Price
Keyword(s):  
Phase Ii ◽  
Phase Iii ◽  
Line Treatment ◽  
Phase Ii Trials ◽  
First Line ◽  
Hand Foot Syndrome ◽  
Phase Iii Trials ◽  
Grade 3 ◽  
Phase Ii And Iii ◽  
First Line Treatment

e15100 Background: Irinotecan and 5-Fluorouracil based combination is an effective regimen for mCRC. Capecitabine, an oral fluoropyrimidine, is a convenient alternative to intravenous 5- Fluorouracil. This study aims to systematically review all published and unpublished controlled phase II and III trials of XELIRI combination, used in first line treatment of mCRC, reported from 2000–2008, to describe its efficacy and safety. Methods: A literature search of MEDLINE, EMBASE, CINAHL and proceedings from ASCO, ESMO and WGIC was conducted. The primary end point was response rate (RR), secondary endpoints include: time to progression (TTP), overall survival (OS) and toxicity. Results: Thirty non-randomised phase II trials (n = 1380) along with 6 randomised phase II and 3 phase III trials, were included (pooled n = 1478). The daily dose of capecitabine ranged from 1,800 mg/m2 to 2,500 mg/m2 for 7 to 14 days per cycle and the dose of irinotecan varied from 180mg/m2 to 350 mg/m2, over a 3 week period per cycle. Amongst the non-randomised studies, the median patient age was 61 years (53–72).The median RR was 46.75% (25–78%). The median reported TTP was 7.9 months (mo) (5- 9.9 mo) and the median OS was 15.6 months (7–24.8 mo). Grade 3–4 toxicity incidence was: diarrhoea (21.5%), neutropenia (12%), vomiting (12.5%), fatigue (6%) and Hand-foot syndrome (6%). The pooled incidence of febrile neutropenia was 2.5%. Amongst the randomised trials, the comparator regimens were XELOX or FOLFIRI. Median age was 65 years (61–74). RR for XELIRI was 39% (34–56%) compared to 47% (27–61.8%) for the non XELIRI comparator arms. Median reported TTP was 8.2 mo (5.7–12.5 mo) for the XELIRI arms and 9.2 mo for the comparator arms. Conclusions: XELIRI is an effective and feasible regime in the first line management of mCRC. However the optimal role of this combination remains to be established. No significant financial relationships to disclose.

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