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]

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.

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]

Phase II study of bortezomib with cisplatin as first-line treatment of malignant pleural mesothelioma (MPM): EORTC 08052.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7081-7081 ◽  
Author(s):  
Mary O'Brien ◽  
Rabab Mohamed Gaafar ◽  
Sanjaykumar Popat ◽  
Francesco Grossi ◽  
Allan Price ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Single Agent ◽  
Dose Intensity ◽  
Line Treatment ◽  
First Line ◽  
Phase Ii Studies ◽  
Grade 3 ◽  
First Line Treatment

7081 Background: Cisplatin is one of the most active drugs available in MPM while bortezomib has shown some activity in single agent phase II studies against MPM. This was a prospective phase II study of cisplatin and bortezomib (CB) in the first line treatment of MPM. Methods: Patients with histological proven MPM, with performance status (PS) 0/1, were eligible. The doses were cisplatin 75mg/m2 /3 wks and bortezomib 1.3mg/m2 day 1, 4, 8, 11 every 3 wks. The primary end-point was progression free survival rate at 18 wks (PFSR=18). The 2-stage Simon design (a=0.1; b = 0.05, P0=0.50 and P1=0.675) was used. In the first step of the study 37 eligible patients were planned. If more than 19 patients were alive and free of progression at 18 wks the total sample size was increased to 76 eligible patients. Results: Between 2007 and 2010 82 patients were entered. The median follow-up time is 32.3 months The median age was 55 years (range: 22-77yrs), male/female: 55/27 , PS 0/1: 9/73, Stage T1: 10%; T2: 42%, T3: 25%; T4: 23% and N0: 57%; N1: 4%; N2: 33%; N3: 6%. The median number of cycles received was 4 and 38% received 6 cycles. Cisplatin/ bortezomib dose intensity was 98/ 80%. Toxicity (grade 3/4): neutropenia 10%, thrombocytopenia 11%, anaemia 1%. Grade 3-4 hyponatraemia/ hypokalaemia occurred in 46/ and 17%. Grade 2 tinnitus, grade 3 fatigue occurred in 16%, and 12%, of patients. Motor/sensory/other neurotoxicity was grade 1: 6/28/7%, grade 2: 2/26/2% and grade 3: 1/7/2% respectively. There were 2 toxic deaths at 32 and 74 days due to acute pneumonitis and cardiac arrest. The PFRS-18 (including symptomatic progression) was 53% (80% confidence intervals, CI, 42-64%). The overall survival was 13.5 months (95% CI 10.5-15) with 56% (95% CI 44-66%) alive at 1 year. The PFS was 5.1 months (95% CI 3.3-6.5). Conclusions: On the basis of the PFRS-18, the null hypothesis could not be rejected, although CB gave predictable toxicity and was as active as other reported regimens in MPM.

Toxicity and outcome data in a phase II study of weekly docetaxel in combination with erlotinib in recurrent and/or metastatic breast cancer (MBC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10623-10623 ◽  
Author(s):  
H. Kaur ◽  
P. Silverman ◽  
D. Singh ◽  
B. W. Cooper ◽  
P. Fu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Treatment Plan ◽  
Single Agent ◽  
Active Agent ◽  
Metastatic Breast ◽  
Hematologic Toxicity ◽  
Egfr Inhibition ◽  
Weekly Docetaxel ◽  
Grade 3

10623 Background: Single agent weekly docetaxel (D) is an active agent in the treatment of MBC with response rates of 29% - 53%. Erlotinib (OSI-774, Tarceva) is a tyrosine kinase inhibitor directed against the epidermal growth factor receptor (EGFR), and is overexpressed in 30–40% of breast cancers. EGFR inhibition by erlotinib (E) and its possible modulation of growth factor synthesis by breast cancer (BC) cells is an attractive treatment target. This study was designed to assess the combination of D and E in previously untreated recurrent &/or MBC. Methods: Adult patients (pts) with histologically confirmed BC without prior chemotherapy for recurrence or metastases were eligible. Treatment plan was: D [35 mg/m2 iv infusion weekly x 3 q4wks] and E 150 mg/d uninterrupted (D+E). E was to be continued in 4 week cycles after maximum tumor response or disease stabilization [following a minimum of 6 cycles of D+E]. The overall survival (OS) was estimated by Kaplan-Meier method. Results: 31of 40 planned female pts were enrolled between 12/02 and 9/05. Median age 52 years, range: 29–79. The median number of cycles of D +E received was 4, (range 1–9) and of E following D+E was 4 (range 1–29). The first 26 pts received planned D dose of 35mg/m2. Because of non-hematologic toxicity, trial was subsequently modified to start D at 30mg/m2.11/31 (36%) were not evaluable due to toxicity. Hematologic grade 3 or 4 toxicity was seen in 45% cases. Principal non-hematologic grade 3–4 toxicities included nausea, diarrhea, and constitutional symptoms seen in 30% of the pts. 4/9 pts receiving E after D+E experienced hematologic, hepatic, constitiutional, and eye (1 each) grade 3 toxicity only. Best clinical response in the 20 evaluable pts included; PR 11(55%), SD 7 (35%), PD 2 (10%). OS (n = 31) was 71% at 12mos, 42% at 24 mos with median OS 23 mos. Conclusions: Combination therapy of advanced breast cancer with Docetaxel and Erlotinib showed promising activity with favorable response compared to other studies. The combination is associated with moderate to severe hematological and non-hematological toxicities. Randomized trials are warranted to further investivate the efficacy of this combination compared to single agent Docetaxel. (Support: Sanofi-Aventis & Genentech.) [Table: see text]

First-line treatment of metastatic breast cancer with weekly abraxane (nab-paclitaxel: a 130 nm albumin-bound paclitaxel particle): A preliminary analysis of the phase II international oncology network ION-04–012 study

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10707-10707 ◽  
Author(s):  
B. Mirtsching ◽  
T. Chidiac ◽  
T. Cosgriff
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
Preliminary Analysis ◽  
Metastatic Breast ◽  
Line Treatment ◽  
First Line ◽  
Grade 3 ◽  
First Line Treatment ◽  
Patient Accrual

10707 Background: Abraxane (paclitaxel protein-bound particles) by intravenous weekly administration schedule has been demonstrated to be active and well tolerated in patients with metastatic breast cancer (MBC) refractory to prior taxane therapy. The purpose of this Phase II, open-label, non-randomized study is to evaluate the efficacy and safety of Abraxane administered weekly to patients with locally-advanced unresectable breast cancer (LABC) or MBC as first-line treatment. Methods: Patients ≥ 18 years with histologically confirmed LABC or MBC received Abraxane (125 mg/m2) by 30 minute IV infusion on days 1, 8, and 15 for the first 3 weeks of each 4-week cycle. HER2-positive patients received concurrent Herceptin given weekly throughout therapy, 4 mg/kg on week 1, and 2 mg/kg on subsequent weeks. Results: From March 11, 2005 to January 4, 2006, 28 patients were enrolled and 27 received study medication (included in this preliminary analysis). Patient accrual continues. Patient characteristics included: gender (M/F) 0/27, median age 60.5 years (range 36–83), ECOG performance status (0–1) 13/14, and HER2 status (±/missing) 6/18/3. A total of 285 cycles have been administered (median 3 [range 1–8]) with a median dose of 125 mg/m2 (range 0–130 mg/m2) and 6 dose modifications have occurred due to toxicity. Eighteen patients are still on study. CTC hematologic toxicities were grade 3 leukopenia (3.7% of patients) and grade 3 neutropenia (7.4%). Grade 3 nonhematologic toxicities were gastritis (3.7%), peripheral sensory neuropathy (7.4%), arthralgia (3.7%), and bone pain (3.7%). No grade 4 nonhematologic toxicities occurred. Conclusions: Preliminary data show that Abraxane given weekly at 125 mg/m2 (with or without Herceptin) for first-line treatment of MBC is well tolerated. Patient accrual continues in this study. Updated analysis of this study will be provided at the meeting. No significant financial relationships to disclose.

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