Phase II trial of paclitaxel, fluorouracil, and cisplatin in patients with advanced carcinoma of the esophagus.

1998 ◽  
Vol 16 (5) ◽  
pp. 1826-1834 ◽  
Author(s):  
D H Ilson ◽  
J Ajani ◽  
K Bhalla ◽  
A Forastiere ◽  
Y Huang ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Esophageal Carcinoma ◽  
Phase Ii ◽  
Metastatic Disease ◽  
Combination Chemotherapy ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Complete Response Rate ◽  
Squamous Carcinoma ◽  
Complete Response

PURPOSE We have previously identified paclitaxel as an active single agent in the treatment of esophageal cancer. We performed a phase II trial of paclitaxel in combination with cisplatin and fluorouracil (5-FU), conventionally used chemotherapy for esophageal cancer. The antitumor response, toxicity, and survival of patients treated with the three-drug regimen were evaluated. PATIENTS AND METHODS Sixty-one patients with advanced, surgically unresectable, or metastatic squamous cell or adenocarcinoma of the esophagus were treated. No prior chemotherapy was allowed. Thirty patients had adenocarcinoma and 31 patients had squamous cell carcinoma. The majority (47 patients; 77%) had metastatic disease and 14 patients (23%) had an unresectable primary or locally recurrent tumor. Patients received paclitaxel 175 mg/m2 by 3-hour infusion day 1; cisplatin 20 mg/m2 daily days 1 through 5, and 5-FU by continuous infusion at a dose of 1,000 mg/m2 daily days 1 through 5. Because of toxicity observed in the first 10 patients treated, the starting dose of 5-FU was subsequently reduced to 750 mg/m2 daily in the remaining patients. A planned attenuation of cisplatin to 15 mg/m2 daily was made after the first three cycles. Granulocyte colony-stimulating factor (G-CSF) was not routinely administered unless the patient had an episode of febrile neutropenia or prolonged grade 4 neutropenia. Treatment was recycled every 28 days. RESULTS Sixty-one patients completed a median of five cycles, and 60 patients were assessable for response. Major responses were seen in 29 patients (48%; 95% confidence intervals, 35 to 61), which included seven complete responses (12%). Comparable response rates were seen for patients with adenocarcinoma (46%) and those with squamous carcinoma (50%), and for patients with metastatic disease (22 of 46 patients; 48%) and those with locally advanced disease (seven of 14 patients; 50%). A significantly higher complete response rate was observed in patients with squamous carcinoma (20%) compared with those with adenocarcinoma (3%; chi2 P=.04). The median duration of response was 5.7 months (range, 1 to 18.6 months). Median survival was 10.8 months (range, 1.5 to 25 months). Toxicity was severe but manageable with dose attenuation, and included 18% of patients with grade 3 neurologic toxicity. Twenty-eight patients (46%) required a dose attenuation for toxicity, and 42 of 275 treatment cycles (15%) required a dose attenuation. Twenty-nine patients (48%) required hospitalization for toxicity, which included 11 patients for neutropenic fever (18%). There were no treatment-related deaths. CONCLUSION The combination of paclitaxel, cisplatin, and 5-FU has substantial antitumor activity in metastatic esophageal carcinoma, with a remarkable complete response rate noted in patients with squamous carcinoma. Paclitaxel is an important new agent in the treatment of esophageal carcinoma, and further evaluation of this agent in combination chemotherapy is warranted. Given the toxicity associated with the current regimen, the optimal dose and schedule of paclitaxel in combination chemotherapy remain to be established.

Phase II Trial of Doxorubicin and Paclitaxel Plus Granulocyte Colony-Stimulating Factor in Metastatic Breast Cancer: An Eastern Cooperative Oncology Group Study

1999 ◽  
Vol 17 (12) ◽  
pp. 3828-3834 ◽  
Author(s):  
Joseph A. Sparano ◽  
Ping Hu ◽  
Radha M. Rao ◽  
Carla I. Falkson ◽  
Antonio C. Wolff ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Complete Response Rate ◽  
Objective Response ◽  
Metastatic Breast ◽  
Complete Response ◽  
Institutional Setting

PURPOSE: Several groups have reported that the combination of doxorubicin plus paclitaxel given as a 3-hour intravenous (IV) infusion for up to eight cycles produces a high response rate (> 80%) and complete response rate (> 20%) in metastatic breast cancer, but is also complicated by a 20% incidence of congestive heart failure (CHF). The purpose of this phase II trial was to evaluate the antineoplastic activity of the regimen in a multi-institutional setting and to reduce the incidence of cardiotoxicity by limiting treatment to a maximum of six cycles. PATIENTS AND METHODS: Fifty-two patients with advanced breast cancer received doxorubicin (60 mg/m2 by IV injection) followed 15 minutes later by paclitaxel (200 mg/m2 by IV infusion over 3 hours) every 3 weeks for four to six cycles. RESULTS: Objective responses occurred in 25 of 48 assessable patients (52%; 95% confidence interval [CI], 38% to 66%), including four complete responses (8%; 95% CI, 0% to 16%). The median cumulative doxorubicin dose given was 240 mg/m2 (range, 132 to 360 mg/m2). Eleven patients (21%) were documented as having a decrease in the LVEF below normal, including three patients (6%; 95% CI, 0% to 12%) who developed CHF. CONCLUSION: The doxorubicin/paclitaxel regimen that we used is unlikely to produce an objective response rate of more than 70% and a complete response rate of more than 20% in patients with metastatic breast cancer, and proved to be excessively cardiotoxic for use in the adjuvant setting.

The VcR-CVAD Regimen Produces a High Complete Response Rate in Untreated Mantle Cell Lymphoma (MCL): First Analysis of E1405 – A Phase II Study of VcR-CVAD with Maintenance Rituximab for MCL.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1661-1661 ◽  
Author(s):  
Brad S Kahl ◽  
Hailun Li ◽  
Mitchell R Smith ◽  
Randy D. Gascoyne ◽  
Elisabeth Paietta ◽  
...  
Keyword(s):  
Phase Ii ◽  
Research Funding ◽  
Response Rate ◽  
Complete Response Rate ◽  
Phase Ii Study ◽  
Cell Lymphoma ◽  
Complete Response ◽  
Mantle Cell ◽  
Grade 3

Abstract Abstract 1661 Poster Board I-687 Introduction One approach to improving outcomes in Mantle Cell Lymphoma (MCL) is to incorporate newer targeted agents into standard chemotherapy regimens. As the proteasome inhibitor bortezomib (Velcade‘) achieved a 33% response rate in relapsed MCL, we hypothesized that the incorporation of Velcade (Vc) into a modified R-hyperCVAD chemotherapy backbone would result in a high complete response rate (CR). The new regimen, VcR-CVAD, was tested for safety and efficacy in a phase II study within the Wisconsin Oncology Network (UW) and demonstrated a CR rate of 77% (Kahl, ASH 2008). To determine the safety and efficacy of this regimen in a cooperative group setting, we initiated E1405: a phase II study of VcR-CVAD with maintenance rituximab (MR) for untreated MCL. Methods Eligible patients had histologically confirmed, previously untreated MCL, PS 0-2, and adequate end organ function. The treatment plan included: Velcade 1.3 mg/m2 days 1 and 4, rituximab 375 mg/m2 IV day 1, cyclophosphamide 300 mg/m2 IV over 3 hrs q 12 hrs X 6 doses days 1-3, doxorubicin 50 mg/m2 continuous infusion over 48 hrs days 1-2, vincristine 1 mg IV day 3, dexamethasone 40 mg po days 1-4. Cycles were repeated every 21 days for 6 cycles and all patients received G-CSF support. Patients achieving SD, PR, or CR received MR administered as 4 weekly treatments every 6 months for 2 years (protocol therapy). Patients had an option to receive high dose chemotherapy and autologous stem cell transplantation (off protocol) rather than MR. The primary endpoint of the trial was the CR rate, incorporating PET imaging, to VcR-CVAD induction therapy. Results Seventy-six eligible patients were enrolled between 5/07 and 10/08. Baseline characteristics include median age 62 (40-76), 59M:17F, 91% stage III/IV, and 39% with elevated LDH. Sixty-four patients (84%) completed VcR-CVAD induction therapy. Reasons for treatment discontinuation included PD (1), toxicity (4), patient preference (2), and other/unknown (5). Response information is available on 74 patients while data is outstanding on 2 patients. The ORR was 96% (73/76; 95% CI, 89%-99%), CR rate 75% (57/76; 95% CI, 64%-84%) and the PR rate 21% (16/76; 95% CI, 13%-32%). Six of the PR patients were coded as such because of protocol violations in which a post-treatment bone marrow biopsy or PET scan was not obtained. The CR rate in the 68 completely restaged patients was 84%. Forty-four patients proceeded to planned MR while 21 patients went off protocol to SCT consolidation. Median follow up is currently too short (9 months) to assess PFS and OS. The major toxicity of the treatment regimen was expected myelosuppression. Grade 3-4 non hematologic toxicities were rare. No patients developed grade 3-4 neuropathy. There were no treatment related deaths. Conclusion The VcR-CVAD induction produced high overall response (96%) and CR rate (75%) in a representative MCL patient population treated on a cooperative group protocol. The CR rate was high and comparable to the UW pilot study (77%). No episodes of severe painful peripheral neuropathy were reported using the reduced vincristine dosage and the overall toxicity profile was very acceptable. Longer follow up is needed to determine if the high CR rate will translate into improved PFS and OS. Disclosures Kahl: Genentech: Consultancy, Research Funding; Millennium: Consultancy, Research Funding. Off Label Use: Bortezomib as front line treatment in MCL. Smith:Genentech: Research Funding; Millennium: Research Funding. Advani:Seattle Genetics, Inc.: Research Funding. Horning:Genentech: Honoraria, Research Funding.

Phase II trial of irinotecan (Ir) plus cisplatin (CDDP) in patients with recurrent or metastatic squamous carcinoma of the head and neck (SCCHN)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 6041-6041
Author(s):  
J. Gilbert ◽  
A. Cmelak ◽  
B. Burkey ◽  
R. Sinard ◽  
W. Yarborough ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Squamous Carcinoma ◽  
Progression Free Survival ◽  
Response Assessment ◽  
Gi Toxicity ◽  
Prognosis Group ◽  
Ecog Ps ◽  
Dose Levels

6041 Background: Prognosis for recurrent or metastatic SCCHN patients remains poor with median survivals of 6–9 months. Therapies targeting this group are needed. We conducted a single arm Phase II trial of Ir plus CDDP in patients with recurrent or metastatic SCCHN. The goal of this trial was to evaluate the efficacy and toxicity of this combination in advanced SCCHN. Methods: Eligible patients had incurable SCCHN, an ECOG PS of 0–2 and were chemonaive (no prior chemotherapy or chemotherapy for primary disease at least 6 months prior to study entry). A two-stage accrual design (Simon) was used. Irinotecan 65 mg/m2 and CDDP 30 mg/m2 were administered weekly for 4 weeks, followed by a 2 week rest for a 6 week cycle. Due to GI toxicity and neutropenia, the Ir was decreased to 50 mg/m2 with CDDP 30 mg/m2. Response assessment was made after every cycle using WHO criteria. The primary endpoint was response rate. Results: Forty patients were enrolled (male: 33, female:7). Median age was 58 (33–79). Forty and 32 patients were evaluable for toxicity and response, respectively. Reasons for unevaluable: 7 without at least 1 full cycle of therapy; 1 patient with incomplete records. Overall response rate was 34% (11/32 PR) with 18% SD (6/32). Median progression free survival was 2.6 months. The median overall survival was 8.2 months. Toxicity was substantial at Ir 65 mg/m2 with a rate of Grade (G) 3 or 4 toxicity of 82% compared to 56% at Ir 50 mg/m2. For both dose levels, G 3 or 4 nausea and vomiting (23%), diarrhea (15%) and neutropenia (35%) were the most common toxicities. Conclusions: The combination of irinotecan and cisplatin is active in a poor prognosis group of patients. Toxicity of irinotecan at 65 mg/m2 with CDDP 30 mg/m2 is substantial. Irinotecan 50 mg/m2 and CDDP 30 mg/m2 is tolerable and provides a 34% response rate. No significant financial relationships to disclose.

Bortezomib Added to R-CVP Is Safe and Effective for Previously Untreated Advanced-Stage Follicular Lymphoma: A Phase II Study by the National Cancer Institute of Canada Clinical Trials Group

2011 ◽  
Vol 29 (25) ◽  
pp. 3396-3401 ◽  
Author(s):  
Laurie H. Sehn ◽  
David MacDonald ◽  
Sheldon Rubin ◽  
Guy Cantin ◽  
Morel Rubinger ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Phase Ii ◽  
Response Rate ◽  
Complete Response Rate ◽  
Standard Dose ◽  
Complete Response ◽  
Phase Iii ◽  
High Risk Population ◽  
Advanced Stage ◽  
Grade 3

Purpose Bortezomib has demonstrated promising activity in patients with follicular lymphoma (FL). This is the first study to evaluate the safety and efficacy of bortezomib added to rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP) in previously untreated advanced-stage FL. Patients and Methods This is a phase II multicenter trial adding bortezomib (1.3 mg/m2 days 1 and 8) to standard-dose R-CVP (BR-CVP) for up to eight cycles in patients with newly diagnosed stage III/IV FL requiring therapy. Two co-primary end points, complete response rate (complete response [CR]/CR unconfirmed [CRu]) and incidence of grade 3 or 4 neurotoxicity, were assessed. Results Between December 2006 and March 2009, 94 patients were treated with BR-CVP. Median patient age was 57 years (range, 29 to 84 years), and the majority had a high (47%) or intermediate (43%) Follicular Lymphoma International Prognostic Index score. BR-CVP was extremely well tolerated, with 90% of patients completing the intended eight cycles. No patients developed grade 4 neurotoxicity, and only five of 94 patients (5%; 95% CI, 0.8% to 9.9%) developed grade 3 neurotoxicity, which was largely reversible. On the basis of an intention-to-treat analysis, 46 of 94 patients (49%; 95% CI, 38.8% to 59.0%) achieved a CR/CRu, and 32 of 94 patients (34%) achieved a partial response, for an overall response rate of 83% (95% CI, 75.4% to 90.6%). Conclusion The addition of bortezomib to standard-dose R-CVP for advanced-stage FL is feasible and well tolerated with minimal additional toxicity. The complete response rate in this high-risk population compares favorably to historical results of patients receiving R-CVP. Given these results, a phase III trial comparing BR-CVP with R-CVP is planned.

scholarly journals A New Light-Emitting, Fabric-Based Device for Photodynamic Therapy of Actinic Keratosis: Protocol for a Randomized, Controlled, Multicenter, Intra-Individual, Phase II Noninferiority Study (the Phosistos Study) (Preprint)

2018 ◽  
Author(s):  
Anne-Sophie Vignion-Dewalle ◽  
Henry Abi Rached ◽  
Elise Thecua ◽  
Fabienne Lecomte ◽  
Pascal Deleporte ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Phase Ii ◽  
Actinic Keratosis ◽  
Response Rate ◽  
Complete Response Rate ◽  
Red Light ◽  
Complete Response ◽  
Light Emitting ◽  
Randomized Controlled ◽  
Individual Phase

BACKGROUND Actinic keratosis (AK) is a common early in situ skin carcinoma caused by long-term sun exposure and usually develops on sun-exposed skin areas. Left untreated, AK may progress to squamous cell carcinoma. To prevent such risk, most clinicians routinely treat AK. Therapy options for AK include cryotherapy, topical treatments, curettage, excision surgery, and photodynamic therapy (PDT). OBJECTIVE The aim of this study is to assess the noninferiority, in terms of efficacy at 3 months, of a PDT protocol involving a new light-emitting device (PDT using the Phosistos protocol [P-PDT]) compared with the conventional protocol (PDT using the conventional protocol [C-PDT]) in the treatment of AK. METHODS In this randomized, controlled, multicenter, intra-individual, phase II noninferiority clinical study, subjects with AK of the forehead and scalp are treated with P-PDT on one area and with C-PDT on the contralateral area. In both areas, lesions are prepared and methyl aminolevulinate (MAL) is applied. Thirty minutes after MAL application, the P-PDT area is exposed to red light at low irradiance (1.3 mW/cm2) for 2.5 hours so that a light dose of 12 J/cm2 is achieved. In the control area (C-PDT area), a 37 J/cm2 red light irradiation is performed 3 hours after MAL application. Recurrent AK at 3 months is retreated. The primary end point is the lesion complete response rate at 3 months. Secondary end points include pain scores at 1 day, local tolerance at 7 days, lesion complete response rate at 6 months, cosmetic outcome at 3 and 6 months, and patient-reported quality of life and satisfaction throughout the study. A total of 45 patients needs to be recruited. RESULTS Clinical investigations are complete: 46 patients were treated with P-PDT on one area (n=285 AK) and with C-PDT on the contralateral area (n=285 AK). Data analysis is ongoing, and statistical results will be available in the first half of 2019. CONCLUSIONS In case of noninferiority in efficacy and superiority in tolerability of P-PDT compared with C-PDT, P-PDT could become the treatment of choice for AK. CLINICALTRIAL ClinicalTrials.gov NCT03076892; https://clinicaltrials.gov/ct2/show/NCT03076892 (Archived by WebCite at http://www.webcitation.org/779qqVKek) INTERNATIONAL REGISTERED REPOR DERR1-10.2196/12990

Increased Dose Rituximab Followed by Maintenance Rituximab As Initial Therapy for Indolent B Cell Lymphomas: A Phase II Trial,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3716-3716
Author(s):  
Jeffrey A. Barnes ◽  
Kristen Stevenson ◽  
Ephraim P. Hochberg ◽  
Tak Takvorian ◽  
David C. Fisher ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
B Cell ◽  
Phase Ii ◽  
Progressive Disease ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Complete Response ◽  
Low Grade ◽  
B Cell Lymphomas ◽  
Grade 3

Abstract Abstract 3716 Background: Rituximab monotherapy as initial treatment for low-grade B-cell lymphomas produces responses in approximately 70% of patients with one third achieving a complete response, and progression-free survival (PFS) of approximately 2 years. Maintenance rituximab appears to prolong initial remissions after rituximab alone. Current dosing for rituximab is largely empiric, so we sought to investigate whether increased doses of rituximab induction would increase the complete response rate (CRR) over that expected from standard dose rituximab. We also sought to assess whether high-dose induction followed by standard maintenance would produce a PFS comparable with that of combination chemoimmunotherapy strategies. Methods: We conducted a phase II trial of increased-dose rituximab monotherapy induction, followed by a standard maintenance schedule. Eligible patients were adults with previously untreated low-grade B-cell lymphomas with measurable disease >2cm and were not candidates for potentially curative radiotherapy to localized disease. Subjects were treated with induction rituximab at a dose of 750 mg/m2 on days 1,8,15, and 22. Patients without progressive disease were then treated with maintenance rituximab at 375mg/m2 every 3 months for 8 doses or until disease progression. The primary end point was CRR as defined by the International Workshop Response Criteria (1999). Secondary endpoints included overall response rate (ORR), PFS, and toxicity. The study was designed with 90% power to show a 50% CRR, with a 30% CRR considered unworthy of further study. Results: Between August 2009 and August 2010, 40 eligible subjects were enrolled (31 grade 1–2 follicular lymphomas, 4 marginal zone lymphomas, 3 small lymphocytic lymphomas, and 2 indolent B cell lymphoma not otherwise specified). The median age was 60 (range 36–88) All subjects had advanced Ann Arbor stage disease. Twenty-two subjects (55%) had involvement of >4 nodal sites, 6 (15%) had a Hgb <12 and 9 (23%) had an elevated LDH. Six subjects (15%) were low risk by the follicular lymphoma prognostic index(FLIPI), 15 (38%) were intermediate risk, and 17 (43%) were high risk. The FLIPI was not available for 2 patients. One patient was not evaluable for the 4 week response assessment in induction due to withdrawal of consent after 3 weeks of therapy. After induction therapy, 1 subject had a CR (3%), 18 had a PR (46%), and 20 had SD (51%). No subjects had progressive disease after induction and all evaluable patients had a reduction in tumor size. With a median number of 4 (range 1–6) maintenance cycles, the CRR increased to 30%, with PRR of 38% and SD in 15% (fig. 1). The PFS at 12 months was 89% [95% CI, 73– 96]. A total of 5 subjects progressed during maintenance therapy, 2 subjects after 3 cycles, 1 after 2 cycles and 2 after 1 cycle. Treatment was well tolerated with only 3 cases (7.5%) of grade 3/4 neutropenia. Twenty three (58%) subjects had allergic reactions with infusions but only 2 (5%) were grade 3 reactions. Conclusions: Increased dose rituximab monotherapy is well tolerated, but does not improve the CRR compared to what would be expected from rituximab at standard doses. Significant improvement in the CRR occurred with ongoing maintenance therapy, and the vast majority of patients remain in remission after 1 year. Ongoing follow-up will determine whether this approach produces a PFS comparable to a chemoimmunotherapy treatment program. Disclosures: Hochberg: Genentech: Consultancy. Fisher:Genentech: Consultancy. Abramson:Genentech: Consultancy.

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