A phase Ib/II study of eribulin with cyclophosphamide (EC) in patients (pts) with advanced breast cancer (ABC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13079-e13079
Author(s):  
Ozge Gumusay ◽  
Jonathan R. Renslo ◽  
Chiara A. Wabl ◽  
Amy Jo Chien ◽  
Michelle E. Melisko ◽  
...  
Keyword(s):  
Phase Ii ◽  
Single Agent ◽  
Complete Response ◽  
Maximum Tolerated Dose ◽  
Primary Objective ◽  
Cycle Phase ◽  
Microtubule Inhibitor ◽  
Phase Ib ◽  
Duration Of Response ◽  
Heavily Pretreated

e13079 Background: Eribulin is an effective microtubule inhibitor for the treatment of ABC. Based on encouraging efficacy with docetaxel/cyclophosphamide, we hypothesized that eribulin combined with cyclophosphamide (EC) would be effective with tolerable toxicity. The aim of the study was to determine the maximum tolerated dose (MTD) of EC, followed by a dose expansion study to estimate the clinical benefit rate (CBR) of EC in pts with ABC. Methods: Study eligibility included pts with histologically confirmed ABC with any number of prior lines of therapy. Pts were treated using a dose escalation strategy with cohort expansion once MTD was determined. Dose level 0 (DL0): E 1.1 mg/m2 on days 1 and 8, C 600 mg/m2 on day 1 of a 21-day cycle. DL1: E 1.4 mg/m2 on days 1 and 8, C 600 mg/m2 on day 1 of a 21-day cycle. Phase II expanded enrollment at DL1. The primary objective of the phase II study was CBR [(complete response (CR), partial response (PR), and stable disease (SD)]. Secondary objectives were response rate (RR), duration of response (DOR), time to progression (TTP), and safety. Using a 2-stage design, responses in 3 of the first 22 pts allowed continued enrollment to a planned 40. Results: No dose limiting toxicities (DLT) were identified in phase Ib (n = 6). 3 pts were treated at DL0 and 3 at DL1, the MTD. 44 pts with ABC were enrolled at the MTD and are included in the analysis. 31 pts had HR+/HER2- disease, 12 pts had triple negative disease (TNBC), 1 pt had HR+/HER2+ disease. Median age was 56 yrs, prior treatment (rx) for ABC included a median of 1 line of hormone rx (range 0-6) and 2 lines of prior chemorx (range 0-7). CBR was 79.5% (35/44; 7 PR, 28 SD) and median PFS 16.4 wks (95%CI:13.8-21.1 wks). Longer PFS was observed in those with HR+ disease vs TNBC (18.1 vs 10.8 wks; P = 0.067). Adverse events (AE) of any grade included fatigue (68.2%, n = 30), neutropenia (ntp) (59.1%, n = 26), nausea (56.8%, n = 25), constipation (50%, n = 22), peripheral neuropathy (47.7%, n = 21), dyspnea (40.9%, n = 18), headache (36.4%, n = 16), and anorexia (36.4%, n = 16). The most common grade 3/4 AE ntp (47.7%, n = 21); 3 pts had febrile ntp. Dose reductions due to ntp were required to 500 mg/m2 C (n = 17) and to 1.1 mg/m2 in eribulin (n = 12). Conclusions: EC in heavily pretreated ABC resulted in an encouraging CBR of 79.5% and PFS of 16.4 wks, comparing favorably to single agent E (PFS 14.8 wks). Dose reduction and delays were due primarily to ntp. EC is an effective combination therapy with manageable toxicity in ABC. Clinical trial information: NCT01554371 .

Phase I evaluation of AZD2171, a highly potent and selective inhibitor of VEGFR signaling, in combination with selected chemotherapy regimens in patients with advanced solid tumors

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3034-3034 ◽  
Author(s):  
P. M. Lorusso ◽  
E. Heath ◽  
M. Valdivieso ◽  
M. Pilat ◽  
A. Wozniak ◽  
...  
Keyword(s):  
Phase I ◽  
Solid Tumors ◽  
Growth Factor Receptor ◽  
Complete Response ◽  
Maximum Tolerated Dose ◽  
Primary Objective ◽  
Selective Inhibitor ◽  
Minor Response ◽  
Heavily Pretreated ◽  
Grade 3

3034 Background: AZD2171 is an oral, potent, selective inhibitor of vascular endothelial growth factor receptor (VEGFR). Trials have demonstrated that inhibition of the VEGF pathway, in combination with certain chemotherapy, provides benefit to patients with a broad range of solid tumors. Methods: This Phase I trial was conducted in heavily pretreated solid tumor patients. In a single protocol, escalating doses of AZD2171 were evaluated (20, 30 and 45 mg) in combination with four separate chemotherapy regimens: mFOLFOX6 (oxaliplatin 85 mg/m2; 5-FU 400 mg/m2; leucovorin 400 mg/m2 q2 weeks; Arm 1); irinotecan 300 mg/m2 q3 week (Arm 2); docetaxel 75 mg/m2 (Arm 3) and pemetrexed 500 mg/m2 (Arm 4). The primary objective was to evaluate safety and tolerability of the combinations and secondary objective to evaluate pharmacokinetic (PK) interaction and clinical efficacy. Maximum tolerated dose (MTD) toxicity was defined through two cycles. Results: 46 patients have been enrolled: 28/35 evaluable for efficacy/toxicity. The MTD has been reached in two arms: Arm 2 - 20 mg AZD2171 and Arm 4 - 30 mg AZD2171. Arm 3 enrollment continues at 45 mg AZD2171. Two dose-limiting toxicities (DLTs) were observed in eight patients at 30 mg AZD2171 in Arm 1. Enrollment of an additional cohort of less heavily pre-treated patients is ongoing to determine the tolerability of 30 mg AZD2171 with FOLFOX. DLTs have included grade 3 fatigue in Arms 1, 2 & 4; grade 3 diarrhea in Arm 1; grade 3 hand-foot syndrome & grade 4 neutropenic fever in Arm 2; and grade 3 hypertension in Arm 4. AZD2171 did not appear to have a major effect on the PK profile of any chemotherapy regimen tested. Steady-state values are comparable with AZD2171 monotherapy. There have been 13 responses (minor response, n=5; partial response, n=6; complete response, n=2; stable disease ≥ 4 cycles, n=6) in heavily pretreated patients, some having demonstrated resistance to identical chemotherapies. Duration of response has been impressive (4-22+ cycles). Conclusions: AZD2171 combinations have been well tolerated with expected toxicities and encouraging responses. [Table: see text]

Pemetrexed in combination with paclitaxel: A phase I clinical and pharmacokinetic trial in patients with solid tumors

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 2051-2051 ◽  
Author(s):  
T. Graefe ◽  
C. Bolling ◽  
C. Lubbing ◽  
J. Latz ◽  
J. Blatter ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Thyroid Carcinoma ◽  
Phase Ii ◽  
Single Agent ◽  
Maximum Tolerated Dose ◽  
Primary Objective ◽  
Recommended Dose ◽  
Clinical Activity ◽  
Best Response ◽  
Recommended Phase Ii Dose

2051 Background: Pemetrexed (Alimta [AL]) and paclitaxel (P) are clinically active in a variety of tumors. The primary objective of this trial was to determine the maximum tolerated dose (MTD) of the ALP combination; secondary objectives were: determination of dose-limiting toxicities (DLTs), definition of a recommended phase II dose, pharmacokinetic (PK) characterization and the anecdotal collection of antitumor activity. Methods: Escalating doses of P (3h infusion, d1 and d8) and AL (10 min infusion, d8 prior to P) were given in a 21d cycle. Results: 59 patients (pts) were enrolled. DLTs occurred at the following ALP (mg/m2) doses: 400/30 [G3 bilirubin (b), G3 and G4 thrombocytopenia (plts)]; 500/30 (G4 plts); 500/40 (G3 b); 500/75 (G4 ANC); 500/100 (G4 leukopenia, G4 ANC). With G4 leukopenia and G4 ANC in 4/6 pts and febrile neutropenia in 1 pt, the MTD was reached at the ALP (mg/m2) dose of 500/120. To confirm safety at the recommended dose-level, another 6 patients were treated at the ALP (mg/m2) dose of 500/100. 18 pts [mesothelioma (3), esophagus (2), lung (1), liver (1), renal (1), stomach (1), thyroid (9)] showed stable disease as best response. 4/14 (29%) pts with thyroid carcinoma showed long lasting partial responses [duration (months) 29+, 22, 18, 15]. One additional PR (2) was observed in a pt with penile carcinoma. AL PK when administered with P were consistent with those for AL administered as a single-agent. Conclusions: The ALP combination is safe and shows broad clinical activity. 500/100 mg/m2 is the recommended dose for further studies. Promising antitumor activity was observed in thyroid cancer. A phase II trial in thyroid carcinoma will be conducted. [Table: see text]

IMAGE, a randomized phase Ib/II study of elisidepsin (E) as a single agent in pretreated advanced gastroesophageal (GE) cancer.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 92-92 ◽  
Author(s):  
Ramon Salazar ◽  
Jean Philippe Metges ◽  
David Alan Anthoney ◽  
Gianluca Laus ◽  
Maria Alsina Maqueda ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Phase Ii ◽  
Single Agent ◽  
Progression Free Survival ◽  
Optimal Dose ◽  
Primary Objective ◽  
Phase Ib ◽  
Flat Dose

92 Background: E is a new marine compound with broad in vitro/in vivo antitumor activity. Low μM concentrations lead to cell-death through membrane permeabilization. E has shown evidence of activity in pre-treated GE patients (pts) in phase I trials. Methods: The primary objective was to determine the tolerability and efficacy of E in pts with GE cancer after 1-2 prior chemotherapy (CT) lines. Initially, dose was optimized (Phase Ib) in two different schedules: a fixed flat dose (FD) of intravenous (i.v) E (8 and 10 mg), in 24h, biweekly (Arm A) and i.v E (3.0 and 3.75mg), in 3h, weekly (Arm B). After dose optimization patients were included and stratified by histology to each optimal dose (Phase II) to determine the rate of progression-free survival at week 16 ± 1 (PFS4) in an intention to treat analysis. If at least two out of 15 pts reached PFS4, recruitment would continue to a maximum of 40 pts per arm. Results: A total of 45 pts were recruited, 12 pts into Phase Ib (Arm A/B: 6/6 pts) and 33 pts into Phase II (Arm A/B: 15/18 pts). Median age was 60 years (35–81 years), 39 were males and ECOG PS was 1 in 75% of pts. Tumour sites were gastric (32% pts), esophageal (39% pts) and esophago-gastric junction (30% pts). Ninety percent of pts had metastatic disease, 31.8% of which had liver metastasis; 55% of pts had two prior lines of CT . No DLTs occurred during the first cycle in the Phase Ib. The optimal dose for Arm A was 10 mg FD, 24h, biweekly; the optimal dose for Arm B was 3.75mg FD, 3h, weekly. Two patients reached PFS4 in Phase Ib (Arm A). Only one patient reached PFS4 in Phase II (Arm A). No objective responses were observed. Therefore, protocol criteria for further recruitment were not met. The safety profile showed grade 1-2 toxicity pruritus (29.5%), nausea (15.9%), vomiting (6.8%) and fatigue (25%). Grade 3-4 toxicity consisted of asymptomatic reversible liver enzyme increases in 20.5% of patients. Conclusions: E is a very tolerable drug with a unique mechanism of action. In the current setting of non-stratified advanced GE patients, E has insufficient antitumor activity to warrant further investigation. Clinical trial information: 2010-020325-40.

Preliminary data from a phase II study of cetuximab with irinotecan in heavily pretreated patients with epidermal growth factor (EGFR)-expressing metastatic colorectal cancer (mCRC): LABEL

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14521-14521 ◽  
Author(s):  
A. Buzaid ◽  
C. de Cerqueira Mathias ◽  
F. Perazzo ◽  
S. Simon ◽  
L. Fein ◽  
...  
Keyword(s):  
Latin American ◽  
Phase Ii ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Treatment Regimens ◽  
Duration Of Response ◽  
Heavily Pretreated ◽  
Grade 3

14521 Background: Cetuximab (Erbitux) is a monoclonal antibody directed against EGFR that is active in combination with irinotecan in patients (pts) with mCRC, who have progressed during or after a prior irinotecan therapy. Methods: This open, single-arm phase II Latin American study investigated this combination in pts with EGFR-expressing mCRC progressing on or within 3 months of chemotherapy containing at least 6 weeks (w) of irinotecan-based therapy. The primary objective was to assess the best overall confirmed response rate (RR). Sample size calculations were based on an expected rate of 20% (±8%). Planned enrollment was 100 pts. Secondary objectives were to explore the duration of response (DOR), progression-free survival (PFS) time, the 12-week PFS rate, and overall survival time. Pts were treated with cetuximab (initial dose 400 mg/m2 then 250 mg/m2 weekly), plus irinotecan at the same dose and schedule (including dose reductions) as pre-study. Preliminary Results: Of 151 pts from 14 centers screened and in the database, 106 (70%, 3 pts missing) were EGFR-expressing and, of these, 79/106 (75%) were treated on-study. Forty (51%) were male; median age was 59 years [27–82]; 70 (89%) pts had a Karnofsky performance status = 90 and 9 (11%) pts = 80. Nineteen (24%) pts had received = 3 prior treatment regimens, 42 (53%) were previously treated with an oxaliplatin-based regimen for metastatic disease. The confirmed overall RR was 26.6% [17.3–37.7]. Median DOR was 23.9 w [17.1–30], median PFS time was 17.7 w [11.7–18.9], and the 12-week PFS rate was 58% [47–69]. Thirty-three (42%) pts were alive at data cut-off. Median survival was 9.7 months [7.9–13.1]. Treatment was well tolerated with the most common grade 3/4 adverse events including: diarrhea, 20%; neutropenia,10%; acne-like rash, 9%. No grade 3/4 infusion-related reactions were reported. Conclusions: The overall confirmed RRs observed in this heavily pretreated population fully met the expectations for the primary endpoint of this study. LABEL confirmed in a Latin American setting the activity and safety of cetuximab plus irinotecan seen in previous studies. No significant financial relationships to disclose.

Phase II study of copanlisib (BAY 80-6946) in combination with gemcitabine and cisplatin in advanced cholangiocarcinoma.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. TPS525-TPS525 ◽  
Author(s):  
Rutika Jitesh Mehta ◽  
Dae Won Kim ◽  
Heloisa P. Soares ◽  
Jongphil Kim ◽  
Richard D. Kim
Keyword(s):  
Phase Ii ◽  
Progression Free Survival ◽  
Complete Response ◽  
Maximum Tolerated Dose ◽  
Primary Objective ◽  
Current Standard ◽  
Standard Regimen ◽  
Stage Design ◽  
Treatment Naïve ◽  
Gemcitabine And Cisplatin

TPS525 Background: The current standard of treatment for cholangiocarcinoma (CCA) is gemcitabine and cisplatin that favored both overall survival (OS) and progression free survival (PFS) when compared to gemcitabine alone. The survival however remains less than than 1 year. Predominant activation of PI3K/AKT signaling pathway is seen in cell line and human tumors of CCA promoting tumorigenesis and increased resistance to radiation and chemotherapy. Inhibition of this pathway sensitizes CCA cells to therapies. Copanlisib is a selective and reversible pan-class I PI3K inhibitor. In preclinical studies, copanlisib demonstrated anti-tumor activity in PIK3CA mutated cells particularly in BC. In a Phase I study, 4 treatment naïve patients with CCA showed response, including 1 complete response. The maximum tolerated dose of copanlisib was determined to be 0.8 mg/kg in this study. We hypothesize that the addition of copanlisib to gemcitabine + cisplatin will enhance the efficacy of the current standard regimen in advanced CCA. Tumor tissue will be collected on every patient for PTEN immunohistochemical staining and NGS analysis using a 26-genes panel. Methods: This is a single institution phase II single arm two-stage design trial using copanlisib in combination with gemcitabine and cisplatin in patients with advanced CCA. Eligible patients include those diagnosed with advanced, unresectable CCA that are treatment naïve or should have received adjuvant treatment more than 6 months prior to initiating the trial. Patients will be treated with Cisplatin (25 mg/m2) plus Gemcitabine (1000 mg/m2) and Copanlisib (60 mg) on days 1 and 8 on a 21 days cycle. Primary objective of the study is PFS at 6 months with secondary objectives being response rate, median PFS, OS, safety and tolerability. Accrual began on June 28, 2016, with planned enrollment for 25 patients. 14 eligible patients will be enrolled in the first stage. If 8 or more patients (≥57%) are alive and progression free at 6 months, an additional 11 patients will be enrolled in the second stage. 11 patients have been enrolled until now. After 3 cycles, response and progression will be evaluated using RECIST v1.1. Clinical trial information: NCT02631590.

Clofarabine (CLO) Is Active in Patients (pts) with Refractory and/or Relapsed Non-Hodgkin’s Lymphoma (NHL): A Phase I/II Study.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4462-4462
Author(s):  
Chadi Nabhan ◽  
Walter Fried ◽  
Angel G. Galvez ◽  
Parameswaran Venugopal ◽  
Phillip Gozun ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Performance Status ◽  
Pneumocystis Carinii ◽  
Standard Of Care ◽  
Complete Response ◽  
Median Number ◽  
Bulky Disease ◽  
Duration Of Response ◽  
Heavily Pretreated

Abstract There is no known standard of care for pts with relapsed and/or refractory NHL who cannot undergo stem cell transplantation (SCT) or have relapsed after SCT. Such pts are candidates for new therapies. CLO is a novel nucleoside analogue with known activity in acute leukemia and myelodysplasia. Previous clinical trials with CLO have established safety and potential activity in a variety of tumors. We performed a phase I/II study of CLO in a heavily pretreated pt population with refractory and/or relapsed NHL regardless of cell type, histology, or grade. Eligible pts were adults over 18 years of age who have relapsed and/or refractory NHL with measurable disease. Pts were required to have adequate performance status, bone marrow function (unless cytopenias were related to disease involvement), renal, cardiac, and liver functions. Pts with bulky disease (>10 cm at any site), known HIV, or immune-related cytopenias were excluded. CLO was given as a 1-hour intravenous infusion for 5 consecutive days every 28 days for a maximum of 6-cycles. All enrolled pts received anti-viral and anti-pneumocystis carinii prophylaxis. Growth factors were administered at the investigator’s discretion. Pts were divided into cohorts of 3 each. CLO was given at 4 mg/m2 to the first cohort with escalated doses by 2 mg/m2 increments for each cohort. Once the dose-limiting toxicity (DLT) was reached, the phase II portion of this study was initiated at the dose below the DLT level. All pts were followed until disease progression. To date, 13 pts have been enrolled with 7 on the phase I portion and 6 on the phase II portion. For the phase I portion, the median age was 79 (range: 27–81); the median number of prior therapies was 5 (range: 2–6) with 3 pts having relapsed after prior SCT. The median number of given CLO cycles in the phase I portion was 2 (range: 1–5). The DLT at 6 mg/m2 was thrombocytpenia establishing 4 mg/m2 as the appropriate dose for phase II. For the phase II portion, the median age was 78 (range: 50–83), median number of prior therapies was 2 (range: 1–8). Taken all together (phase I and II pts), 9 out of 13 pts are evaluable for response. (All received at least 1 cycle). There was 1 complete response (CR) and 4 partial responses (PR) for an overall response rate (OR) of 55%. Four patients demonstrated stable disease (SD) with one of them progressing shortly after 2 months. Eight patients remain alive (overall survival: 61%) at a median follow up of 4 months (range: 1–13). Median times to progression and duration of response have not been reached in responding pts. CLO is active in heavily pretreated refractory and/or relapsed NHL. The drug has an acceptable toxicity profile. Myelosuppresion is the major adverse event in this heavily pretreated population. The study continues to accrue patients and will be updated at the meeting.

Phase II Study of Temozolomide in Relapsed or Refractory High-Risk Neuroblastoma: A Joint Société Française des Cancers de l’Enfant and United Kingdom Children Cancer Study Group–New Agents Group Study

2006 ◽  
Vol 24 (33) ◽  
pp. 5259-5264 ◽  
Author(s):  
Hervé Rubie ◽  
Julia Chisholm ◽  
Anne Sophie Defachelles ◽  
Bruce Morland ◽  
Caroline Munzer ◽  
...  
Keyword(s):  
High Risk ◽  
Partial Response ◽  
Phase Ii ◽  
Response Assessment ◽  
Complete Response ◽  
Lesion Size ◽  
Mixed Response ◽  
Duration Of Response ◽  
Heavily Pretreated ◽  
Grade 3

Purpose To determine the response rate (RR) of neuroblastoma (NB) in children to temozolomide (TMZ), and evaluate the duration of response and tolerance of the drug in this patient population. Patients and Methods A multicenter, phase II evaluation of an oral, daily schedule of TMZ (200 mg/m2/d × 5 days every 28 days) was undertaken in children with refractory or relapsed high-risk NB (metastatic or localized with Myc-N amplification). Response assessment was based on imaging with two-dimentional measurement of disease and meta-iodobenzylguanidine (MIBG) score. Activity was defined by a reduction in lesion size or isotope uptake at anytime. Methodology included a two-step design using Fleming’s method with a first step of 15 patients and a second of 10 additional patients if two to four responses had been observed in the first cohort. All data was centrally reviewed by a panel. Results Twenty-five assessable patients were recruited over a 14-month period in 14 centers and received 94 cycles of chemotherapy. Twenty-three patients had metastatic NB either refractory (n = 9) or in relapse (n = 14). Grade 3 or 4 thrombocytopenia was the most frequent toxicity (16% of cycles). Myelosuppression resulted in treatment delays and dose reductions (24% and 21% of cycles, respectively). Response (complete response, very good partial response, or partial response) was observed in five patients (RR = 20% ± 8%) with a median duration of 6 months and an objective or mixed response in five additional patients. Conclusion Temozolomide shows activity in heavily pretreated patients with NB, and deserves further evaluation in combination with another drug.

Assessment of Two Doses of Infliximab in Patients with Low/Intermediate Risk IPSS Myelodysplastic Syndrome (MDS): An EORTC Leukemia Group (LG) Randomized Phase II Trial (06023).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1456-1456
Author(s):  
Liliana Baila ◽  
Stefan Suciu ◽  
Petra Muus ◽  
Sergio Amadori ◽  
Michel Delforge ◽  
...  
Keyword(s):  
Phase Ii ◽  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Single Agent ◽  
Complete Response ◽  
Dose Schedule ◽  
Primary Objective ◽  
Intermediate Risk ◽  
Open Label ◽  
Severe Infections

Abstract Introduction: There is strong evidence that the cytopenia(s) in MDS might be caused by excessive, cytokine induced, intramedullary apoptotic death of progenitor hematopoietic cells. TNFα is a key cytokine that may trigger and sustain the excessive apoptosis processes in early disease. Infliximab is a chimeric human-murine monoclonal antibody with high affinity for human TNFα. Infliximab effectively prevents TNFα specific signaling in immune mediated inflammatory diseases. The therapeutic potential of suppressing TNFα mediated apoptosis in MDS was investigated. Patients and methods: The EORTC LG conducted an open label 2-arm randomized, Simon 2-stage design, phase II study, with the primary objective of assessing the activity of two different dose levels of Infliximab, as single agent, in patients (pts) with low-/intermediate-risk MDS according to IPSS. Activity was assessed by response rate, using the International Working Group criteria: Complete Response (CR) + Partial Response (PR) + Hematological Improvement (HI). Toxicity was assessed as a secondary objective. Results: Between February 2004 and March 2006, 37 eligible/evaluable pts (targeted sample size for the analysis of first stage) were randomly assigned to receive Infliximab, 3 mg/kg (18 pts) vs 5 mg/kg (19 pts), intravenously on days 1 and 15, thereafter every 4 weeks, for a total of 8 courses. Baseline characteristics by treatment arm (3 mg/kg vs 5 mg/kg) were: median age (65 vs 69 years); IPSS risk score: low (2 vs 6 pts), Intermediate-1 (14 vs 10 pts), Intermediate-2 (2 vs 3 pts); cytogenetic risk group: good (9 vs 12 pts), intermediate (5 vs 4 pts), unknown (4 vs 3 pts). Treatment applicability (3 mg/kg vs 5 mg/kg): 20 pts (10 vs 10) completed the 8 cycles of therapy, and 17 pts (8 vs 9) stopped earlier due to: progressive disease (2 vs 4), excessive toxicity (3 vs 0), patient’s refusal (2 vs 2), death due to an unrelated cause (1 vs 1), other reasons (0 vs 2). Activity (3 mg/kg vs 5 mg/kg): 3 pts responded to treatment in the 3 mg/kg arm: 1 CR, 1 PR and 1 HI (neutrophils), while no patient responded in the 5 mg/kg arm. A total of 21 pts (7 vs 14) had stable disease, 11 pts (7 vs 4) had documented disease progression and 2 pts were inevaluable for response (1 vs 1). After a median follow-up of 1.5 years, 8 pts (6 vs 2) died. Adverse events: 3 out of 18 patients died due to infections in the 3 mg/kg arm vs 0/19 in the 5 mg/kg arm. Two of the lethal infections were considered likely related to protocol treatment: one patient developed a fatal mucormycosis during treatment and one patient developed a fatal sepsis shortly after the eighth Infliximab infusion and thereafter also had documented progression to AML. There were few other AE/toxicities. Conclusion: Infliximab in the 3 mg/kg dose/schedule showed some activity in this study. Infliximab has limited activity as single agent but may warrant further investigation in combination with other active agents. Patients must be monitored closely for occurrence of severe infections.

Bendamustine in Patients With Rituximab-Refractory Indolent and Transformed Non-Hodgkin's Lymphoma: Results From a Phase II Multicenter, Single-Agent Study

2008 ◽  
Vol 26 (2) ◽  
pp. 204-210 ◽  
Author(s):  
Jonathan W. Friedberg ◽  
Philip Cohen ◽  
Ling Chen ◽  
K. Sue Robinson ◽  
Andres Forero-Torres ◽  
...  
Keyword(s):  
Phase Ii ◽  
Hodgkin’S Lymphoma ◽  
Single Agent ◽  
Progression Free Survival ◽  
Complete Response ◽  
Hodgkin's Lymphoma ◽  
Patients Âgés ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Duration Of Response

PurposeBendamustine hydrochloride is an alkylating agent with novel mechanisms of action. This phase II multicenter study evaluated the efficacy and toxicity of bendamustine in patients with B-cell non-Hodgkin's lymphoma (NHL) refractory to rituximab.Patients and MethodsPatients received bendamustine 120 mg/m2intravenously on days 1 and 2 of each 21-day cycle. Outcomes included response, duration of response, progression-free survival, and safety.ResultsSeventy-six patients, ages 38 to 84 years, with predominantly stage III/IV indolent (80%) or transformed (20%) disease were treated; 74 were assessable for response. Twenty-four (32%) were refractory to chemotherapy. Patients received a median of two prior unique regimens. An overall response rate of 77% (15% complete response, 19% unconfirmed complete response, and 43% partial) was observed. The median duration of response was 6.7 months (95% CI, 5.1 to 9.9 months), 9.0 months (95% CI, 5.8 to 16.7) for patients with indolent disease, and 2.3 months (95% CI, 1.7 to 5.1) for those with transformed disease. Thirty-six percent of these responses exceeded 1 year. The most frequent nonhematologic adverse events included nausea and vomiting, fatigue, constipation, anorexia, fever, cough, and diarrhea. Grade 3 or 4 reversible hematologic toxicities included neutropenia (54%), thrombocytopenia (25%), and anemia (12%).ConclusionSingle-agent bendamustine produced durable objective responses with acceptable toxicity in heavily pretreated patients with rituximab-refractory, indolent NHL. These findings are promising and will serve as a benchmark for future clinical trials in this novel patient population.

Phase II study of fluorouracil and recombinant interferon alfa-2a in previously untreated advanced colorectal carcinoma.

1990 ◽  
Vol 8 (12) ◽  
pp. 2027-2031 ◽  
Author(s):  
R Pazdur ◽  
J A Ajani ◽  
Y Z Patt ◽  
R Winn ◽  
D Jackson ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Single Agent ◽  
Complete Response ◽  
Interferon Alfa ◽  
Bolus Administration ◽  
Recombinant Interferon ◽  
Duration Of Response ◽  
Advanced Colorectal Carcinoma ◽  
Grade 3

We conducted a phase II clinical trial of fluorouracil (5FU) and recombinant interferon alfa-2a (rIFN alpha-2a) in 52 previously untreated patients with bidimensionally measurable metastatic colorectal cancer. During week 1, 5FU was administered as a continuous intravenous infusion, 750 mg/m2/d for 5 consecutive days. Intravenous bolus administration of 5FU 750 mg/m2 was given weekly for 7 weeks starting on day 12. rIFN alpha-2a (Roferon; Hoffman-LaRoche, Nutley, NJ), 9 x 10(6) U, was administered subcutaneously three times weekly during weeks 1 to 8. Patients were evaluated for response on week 9. Of 52 patients enrolled in the study, 51 were assessable for toxicity, and 45 were assessable for response. Fifteen patients experienced partial response, and one patient achieved a clinical complete response for an overall response rate of 35% (95% confidence interval [CI], 22%, 50%). Median duration of response is 7.5 months (range, 4 to 11 months). Seventy percent of patients entered on the study are alive with a median follow-up duration of 7 months. Twenty-five percent of patients developed grade 4 toxicity, and 82% developed grade 3 toxicity. One drug-related death in the presence of sepsis was reported, and two treatment-related seizures occurred. Our experience with this schedule produced a lower response rate with greater toxicity than previously reported. Current randomized trials comparing this schedule of 5FU with rIFN alpha-2a to 5FU plus folinic acid (leucovorin) or single-agent 5FU may determine its role in the treatment of advanced colorectal carcinomas.

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