Comparison of Results from a Phase 1/2 Study of Lumiliximab (Anti-CD23) in Combination with FCR for Patients with Relapsed CLL with Published FCR Results.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 32-32 ◽  
Author(s):  
John C. Byrd ◽  
Januario Castro ◽  
Susan O’Brien ◽  
Ian W. Flinn ◽  
Andres Forero-Torres ◽  
...  
Keyword(s):  
Response Rate ◽  
Phase 1 ◽  
Performance Status ◽  
Randomized Study ◽  
Complete Response ◽  
Cancer Center ◽  
Published Data ◽  
Hematologic Toxicity ◽  
Variable Regions ◽  
Overall Response

Abstract Lumiliximab is a PRIMATIZED® anti-CD23 monoclonal antibody with human IgG1 constant regions and macaque variable regions. Preclinical data demonstrated that lumiliximab enhanced both fludarabine- and rituximab- mediated apoptosis in CLL cells. Thus, a Phase 1/2, open-label, dose-escalation, multicenter study (Study 152–30) evaluating lumiliximab + fludarabine, cyclophosphamide, and rituximab (L + FCR) for relapsed CD23+ B-cell CLL was initiated. Treatment has been completed and follow-up is ongoing. Thirty-one patients (pts) received either 375 mg/m2 (n=3) or 500 mg/m2 (n=28) of lumiliximab in combination with a 28-day cycle of FCR for up to 6 cycles. Median age at study entry was 58 yrs. The majority of pts (74%) were Rai Stage I/II. The most common adverse events included nausea (77%), pyrexia (61%), chills (55%), neutropenia (55%), and fatigue (48%). Twenty pts (65%) experienced a Grade 3 or 4 event. An overall response rate of 71% was demonstrated: 48% complete response (CR), 10% partial response (PR), and 13% unconfirmed PR. Currently, baseline cytogenetic data is available for 21 pts who received 500 mg/m2 of lumiliximab. Although preliminary, 1 of the 4 pts with del(17p13.1) responded; of the 6 pts with del(11q22.3), 5 responded with 4 attaining a CR. A comparison with published data from a study of FCR alone in 177 pts with relapsed or refractory CLL conducted at the M.D. Anderson Cancer Center (MDACC) (Wierda W, O’Brien S, Wen S, et al. J Clin Oncol.2005;23:4070–4078) demonstrated that L + FCR has an acceptable safety profile, does not appear to increase the toxicity (including myelosuppression) of the FCR regimen, and compares favorably with the CR rate of the FCR regimen alone, as displayed in Table 1. Most pt characteristics (age, gender, median number of prior therapies, and WHO performance status) were similar between the 2 studies; however, more pts in the MDACC study were Rai Stage III-IV (50% vs 22%) and were rituximab-naïve (88% vs 40%). Furthermore, there were no obvious differences in hematologic toxicity between the 2 studies and the tolerability of L + FCR was similar to that of FCR, with approximately 50% percent of pts completing 6 cycles of treatment in both studies. These data suggest that L + FCR may produce a higher complete response rate than FCR without additional toxicity. Based upon this data, a multicenter, global, randomized study of L + FCR vs. FCR alone is being initiated. Table 1. Comparison of Responses in Study 152–30 and the MDACC Study Study 152–30, L + FCR (N=31), n (%) MDACC, FCR (N =177), n (%) 1CR and PR response criteria were the same in both studies. 2PRu is included in the OR. Overall Response 22 (71%) 130 (73%) Complete Response1 15 (48%) 45 (25%) Partial Response1 3 (10%) 85 (48%) Unconfirmed Partial Response2 4 (13%)

scholarly journals Phase 1/2a study of 177Lu-lilotomab satetraxetan in relapsed/refractory indolent non-Hodgkin lymphoma

2020 ◽  
Vol 4 (17) ◽  
pp. 4091-4101
Author(s):  
Arne Kolstad ◽  
Tim Illidge ◽  
Nils Bolstad ◽  
Signe Spetalen ◽  
Ulf Madsbu ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Overall Response Rate ◽  
Response Rate ◽  
Phase 1 ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Hematologic Toxicity ◽  
Overall Response ◽  
Non Hodgkin Lymphoma ◽  
Anti Cd20

Abstract For patients with indolent non-Hodgkin lymphoma who fail initial anti-CD20–based immunochemotherapy or develop relapsed or refractory disease, there remains a significant unmet clinical need for new therapeutic approaches to improve outcomes and quality of life. 177Lu-lilotomab satetraxetan is a next-generation single-dose CD37-directed radioimmunotherapy (RIT) which was investigated in a phase 1/2a study in 74 patients with relapsed/refractory indolent non-Hodgkin B-cell lymphoma, including 57 patients with follicular lymphoma (FL). To improve targeting of 177Lu-lilotomab satetraxetan to tumor tissue and decrease hematologic toxicity, its administration was preceded by the anti-CD20 monoclonal antibody rituximab and the “cold” anti-CD37 antibody lilotomab. The most common adverse events (AEs) were reversible grade 3/4 neutropenia (31.6%) and thrombocytopenia (26.3%) with neutrophil and platelet count nadirs 5 to 7 weeks after RIT. The most frequent nonhematologic AE was grade 1/2 nausea (15.8%). With a single administration, the overall response rate was 61% (65% in patients with FL), including 30% complete responses. For FL with ≥2 prior therapies (n = 37), the overall response rate was 70%, including 32% complete responses. For patients with rituximab-refractory FL ≥2 prior therapies (n = 21), the overall response rate was 67%, and the complete response rate was 24%. The overall median duration of response was 13.6 months (32.0 months for patients with a complete response). 177Lu-lilotomab satetraxetan may provide a valuable alternative treatment approach in relapsed/refractory non-Hodgkin lymphoma, particularly in patients with comorbidities unsuitable for more intensive approaches. This trial was registered at www.clinicaltrials.gov as #NCT01796171.

Treatment of refractory chronic lymphocytic leukemia with fludarabine phosphate via the group C protocol mechanism of the National Cancer Institute: five-year follow-up report.

1997 ◽  
Vol 15 (2) ◽  
pp. 458-465 ◽  
Author(s):  
J M Sorensen ◽  
D A Vena ◽  
A Fallavollita ◽  
H G Chun ◽  
B D Cheson
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
National Cancer Institute ◽  
Response Rate ◽  
Performance Status ◽  
Treatment Protocol ◽  
Complete Response ◽  
Lymphocytic Leukemia ◽  
Motor Dysfunction ◽  
Hematologic Toxicity ◽  
Contributing Factors

PURPOSE To provide fludarabine to physicians for the management of patients with advanced refractory chronic lymphocytic leukemia (CLL) and to determine the response rate and duration, toxicity, and survival with this agent. PATIENTS AND METHODS This phase II protocol was open to all eligible patients whose local physicians obtained written permission from the National Cancer Institute (NCI) to register patients onto this protocol. Of 791 national and international enrolled patients, 724 with a median age of 65 years received fludarabine, of which 703 were assessable for response. RESULTS Thirty-two percent of assessable patients responded (95% confidence interval [CI], 29% to 36%), with 21 patients (3%) obtaining a complete response and 205 (29%) a partial response. The median duration of response was 13.1 months and the median survival time from registration was 12.6 months. Age, performance status (PS), and Rai stage correlated with survival (P < .01). Grade 4 hematologic toxicity was reported in 43% and was associated with infection in 22%. Neurotoxicity (primarily grade 1 motor dysfunction) was reported in 14% patients and correlated with age. CONCLUSION This study describes the toxicity and activity of fludarabine in refractory CLL in a setting that more closely resembles clinical practice than most published trials. The low response rate may be related to advanced stage (89% Rai high-risk), disease-related symptoms (63% had B symptoms), and/or degree of prior treatment. Other contributing factors inherent in a group C treatment protocol included lack of central pathology review, variable supportive care, and a tendency to use this mechanism at a later stage in the disease.

Cyclophosphamide Remains An Important Component of Treatment in CLL Patients Receiving Pentostatin and Rituximab Based Chemoimmunotherapy

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 43-43 ◽  
Author(s):  
Neil E. Kay ◽  
Wenting Wu ◽  
John C. Byrd ◽  
Brian Kabat ◽  
Diane F. Jelinek ◽  
...  
Keyword(s):  
Overall Response Rate ◽  
Response Rate ◽  
Patient Characteristics ◽  
Complete Response ◽  
Hematologic Toxicity ◽  
Overall Response ◽  
Grade 3 ◽  
Ecog Ps ◽  
Experienced Grade

Abstract BACKGROUND: We have previously studied and reported that the combination of pentostatin (P, 2 mg/m2), cyclophosphamide (C 600 mg/m2) and rituximab (R 375 mg/m2) in previously untreated CLL is highly effective with an overall response (OR) rate of over 90% and a complete response rate (CR) of 41% (Blood109:405–411, 2007). We also found that this regimen can be effective even in older patients (&gt;70 y), those with elevated beta-2 microglobulin levels, and patients with mildly reduced creatinine clearances (Cancer. 109:2291–2298, 2007). To determine whether similar benefit could be achieved without inclusion of an alkylating agent, we conducted a follow-up trial testing pentostatin and rituximab without cyclophosphamide and employing a higher pentostatin dose (4 mg/m2). METHODS: Eligible pts had documentation of active CLL by standard NCI-WG criteria, and were previously untreated. Treatment schema consisted of 6 cycles of pentostatin (4 mg/m2) and rituximab given every 21 days. Pentostatin was given on the first day of each cycle following infusion of rituximab. Rituximab was given at 100mg/m2 IV at day 1, then 375 mg/m2 IV on days 3 and 5 of the first treatment cycle. During cycles 2 to 6, Rituximab was given at 375 mg/m2 as a single IV infusion day 1 of week 4, 7, 10, 13 and 16. All patients were staged two months after completion of the 6 cycles of PR using the NCI-WG criteria. PATIENT CHARACTERISTICS: Overall, 33 patients were enrolled at Mayo Clinic and Ohio State University between July 2005 and February 2008. All 33 were eligible: 82% male, median age 65 (range: 45–81), with 9 (27%) being 70 years or older. 76% had a baseline ECOG PS of 0, and the rest were ECOG PS 1. Overall, 36% of patients had intermediate Rai risk (stage I–II) and 63% high Rai risk (stage 3–4) disease. Prognostic testing revealed that 36% were CD38+, 50% were Zap-70 +, and 39% had an unmutated IgVh status. Chromosome analysis by FISH found that 99% had detectable FISH panel defect, including 61%, 27% and 3% of patients with 1, 2, or 3 FISH detects, respectively. RESULTS: 28 of 33 patients (85%) completed therapy. While on treatment, 6 pts (18%) had a dose held or modified with 4 of these delays due to hematologic AE. For adverse events deemed at least possibly related to treatment, 4 (12%) pts experienced grade 3+ hematologic toxicity and 5 (15%) experienced grade 3+ non-hematologic toxicity. Out of all 33 enrolled patients, the overall response rate was 79% with 10 CR, 6 nPR, and 10 PR. At the time of this analysis, 29/33 patients are still alive with a median follow-up time of 14 months on surviving patients. To date 17/33 (52%) of patients have progressed with an estimated median time to progression of 12 months (95% CI: 8.5–21 months). 13/26 responders have progressed. Median duration of response is 12.5 months ((95% CI: 11–21 months). Finally, since eligibility were nearly identical and enrollment accrued at the same two academic centers, we compared the patient characteristics, response rates, and PFS of the 33 patients treated with PR to the 64 patients previously treated on our PCR trial. Patients in the two studies were generally similar with respect to demographic and prognostic characteristics, although patients in the PR trial had higher WBC and were less likely to be IgVH unmutated (Table). Although the differences in ORR and CR rate were not significantly different, the PFS appeared to be inferior in patients treated with PR as compared to PCR (12 months vs. 31 months; p=0.003). CONCLUSION: Although the PR regimen achieves a high OR response rate, the PFS appears inferior to PCR therapy. These findings suggest that increasing the purine nucleoside analogue dose does not eliminate the need to include cyclophosphamide in chemoimmunotherapy for patients with CLL. PCR Trial N=64 PR Trial N=33 P value Age, median(range) 63 years (38–80) 65 years (45–81) 0.34 ≥70 years(%) 28% 27% Male 77% 82% 0.61 Rai stage 0 5% 0 0.46 Rai stage I–II 42% 36% Rai stage III–IV 53% 64% White Cell Count, median(range) 79 × 109/L (11–519) 127 × 109/L (8–430) 0.04 &lt;50 × 109/L 36% 28% 50–149 × 109/L 44% 25% &gt;150 × 109/L 20% 47% Serum B2-microglobulin, median(range) 3.97 (1.8–13.5) 3.80 (2.0–8.2) 0.81 &gt;2 × Upper Limit Normal(%) 57% 58% CD38 Positive 34% 36% 1.00 ZAP-70 Positive 36% 50% 0.26 IgVH Unmutated 71% 39% 0.004 FISH Normal, 11% 9% 13q- 35% 42% +12 21% 24% 6q- 2% 0 11q- 22% 18% 17p- 6% 3% other 3% 3% Overall Response Rate 91% 79% 0.12 Complete Response Rate 41% 30% 0.38 Median PFS 31 months 12 months 0.003

Teniposide and etoposide in previously untreated small-cell lung cancer: a randomized study.

1991 ◽  
Vol 9 (9) ◽  
pp. 1627-1631 ◽  
Author(s):  
E Bork ◽  
J Ersbøll ◽  
P Dombernowsky ◽  
B Bergman ◽  
M Hansen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Performance Status ◽  
Randomized Study ◽  
Complete Response ◽  
Small Cell ◽  
Hematologic Toxicity ◽  
Small Cell Lung ◽  
Highly Active

A randomized study comparing teniposide (VM-26) and etoposide (VP-16) was performed to investigate whether there are any differences in the activity and toxicity of these two analogs in small-cell lung cancer (SCLC). Only previously untreated patients with SCLC were included; 46 and 48 patients receiving VP-16 and VM-26, respectively, are assessable for response. There were no differences between the two groups with respect to extent of disease, median age, and performance status (PS). The initial doses were for both compounds 70 mg/m2 intravenously (IV) daily for 5 days every 3 weeks. After inclusion of 25 patients in the study, the doses were increased to 80 mg/m2 for VM-26 and 90 mg/m2 for VP-16 because of differences in toxicity. VM-26 caused more hematologic toxicity than VP-16 throughout the study. The overall responses (complete response [CR] plus partial response [PR]) were 65% for VP-16 and 71% for VM-26, with CR occurring in 24% and 23%, respectively, for the two compounds. Median survival was 8.5 months for VP-16-treated patients versus 11.3 months for VM-26-treated patients (P = .58). It is concluded that both VP-16 and VM-26 are highly active single agents in SCLC.

Randomized study of continuous infusion fluorouracil versus fluorouracil plus cisplatin in patients with metastatic colorectal cancer.

1990 ◽  
Vol 8 (2) ◽  
pp. 313-318 ◽  
Author(s):  
N Kemeny ◽  
K Israel ◽  
D Niedzwiecki ◽  
D Chapman ◽  
J Botet ◽  
...  
Keyword(s):  
Colorectal Carcinoma ◽  
Partial Response ◽  
Continuous Infusion ◽  
Response Rate ◽  
Performance Status ◽  
Randomized Study ◽  
Hematologic Toxicity ◽  
Partial Response Rate ◽  
Duration Of Response ◽  
Routine Therapy

One hundred twenty-two chemotherapy-naive patients with histologically confirmed colorectal adenocarcinoma were entered into a randomized trial comparing infusional fluorouracil (FU) versus cisplatin (CDDP) and FU. In both groups, patients received continuous infusion FU 1,000 mg/m2/d for 5 consecutive days every 4 weeks. Patients randomized to CDDP/FU also received CDDP 20 mg/m2 intravenous (IV) bolus on days 1 to 5 of each cycle. Patients were comparable in terms of age, performance status, baseline laboratory values, dominant sites of measurable disease, and percent of liver involvement. The partial response rate was significantly greater in patients who received CDDP/FU versus FU alone (25% v 3%, P = .001). Patients who received CDDP/FU experienced significantly greater toxicity compared with FU alone: grades 3 and 4 hematologic toxicity occurred in 22% and 0% of patients, respectively (P = .0001); grades 2 to 4 nausea and vomiting occurred in 80% and 15% of patients, respectively (P = .0001). There were no significant differences in either the duration of response (median, 6 and 4.7 months for CDDP/FU and FU groups, respectively) or survival (median 10, and 12 months, respectively). Compared with infusional FU alone, CDDP/FU provided a significantly greater partial response rate with increased toxicity, but it did not improve overall survival in patients with advanced colorectal carcinoma. Therefore, the use of CDDP/FU as routine therapy for the treatment of colorectal carcinoma cannot be recommended.

Combination of Cyclophosphamide, Adriamycin and Platinum (Cap) versus 5-Fluorouracil, Adriamycin and Cyclophosphamide (Fac) as Primary Treatment in Metastatic Breast Cancer: Results of a Prospective Randomized Study

1989 ◽  
Vol 75 (2) ◽  
pp. 132-136 ◽  
Author(s):  
Krsto Kolarić ◽  
Dunja Vukas ◽  
Vera Potrebica
Keyword(s):  
Breast Cancer ◽  
Soft Tissue ◽  
Response Rate ◽  
Randomized Study ◽  
Metastatic Breast ◽  
Complete Response ◽  
Overall Response ◽  
Visceral Organs ◽  
Remission Duration ◽  
The Difference

Based on favorable results we reported earlier with the CAP regimen in breast cancer (CAP vs CMFVP), the present study compared the CAP with the FAC regimen, which is so far one of the most active adriamycin containing chemotherapy regimens in breast cancer. The aim of the study was to find the optimal first line treatment and possibly evaluate the role of cis platinum in breast cancer chemotherapy. The CAP schedule consisted of cyclophosphamide 200 mg/m2 i.v. days 1, 3 and 5, adriamycin 40 mg/m2 i.v. day 1, and platinum 30 mg/m2 i.v. day 1, 3 and 5. The FAC schedule included 5-FU 500 mg/m2 days 1 and 8, adriamycin 50 mg/m2 day 1, and cyclophosphamide 500 mg/m2 da 1. One hundred and twenty-six previously untreated patients received > 2 cycles and were evaluated. In the CAP arm 15 complete (26%) and 24 partial remissions were observed, resulting in a 67 % overall response rate (39/58). The response in soft tissue and visceral organs was notable (78 % – 22/28, 71 % – 15/21) with an important complete response rate (32 %). In the FAC arm there was an overall response in 41 % (28/68) of patients, with 8 complete (12 %) and 20 partial responses. The difference in overall response, complete response, and response in soft tissue and visceral organs, was statistically significant in favor of the CAP arm (P < 0.005). Concerning bone metastases there was no difference between the two schedules in response rate, nor in the median remission duration (CAP 11, FAC 10 months). In spite of a somewhat longer median survival in the CAP group, the difference (13 months vs 9 months) was not statistically significant (P=0.10). Toxicity was moderate and tolerable in both regimens with more pronounced myelosuppression and vomiting in the CAP group. Compared with the FAC schedule the platinum containing combination chemotherapy (CAP) showed higher antitumor activity with no reflection on remission duration and survival.

scholarly journals A Phase 1 -2 Study of Brentuximab Vedotin (Bv) and Bendamustine (B) in Patients with Relapsed or Refractory Hodgkin Lymphoma (HL) and Anaplastic Large T-Cell Lymphoma (ALCL)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3084-3084 ◽  
Author(s):  
Owen A. O'Connor ◽  
John Kuruvilla ◽  
Ahmed Sawas ◽  
Changchun Deng ◽  
Molly Patterson ◽  
...  
Keyword(s):  
Overall Response Rate ◽  
Response Rate ◽  
Treated Patient ◽  
Phase 1 ◽  
Complete Response ◽  
Brentuximab Vedotin ◽  
Cell Transplant ◽  
Salvage Regimen ◽  
Dose Cohort ◽  
Overall Response

Abstract Patients with relapsed or refractory HL or ALCL have few therapeutic options. Recently, brentuximab vedotin was approved for patients who have relapsed following autologous stem cell transplant (ASCT), and for patients considered ineligible for ASCT. Patients who achieve a complete response experience very durable remissions of their disease. Another agent recently established as active in patients with heavily treated HL is bendamustine, which has been demonstrated to produce a good overall response rate in this setting, though the progression free survival and duration of response are considered modest. The notion that one drug which can produce a rapid response in a majority of patients, coupled with one that can sustain a response led to the concept that a brentuximab vedotin and bendamustine combination could be an excellent salvage regimen for patients with relapsed or refractory disease especially considering their largely non-overlapping toxicity spectra. If this combination produces meaningful complete remissions, it could be used as second line therapy, sparing patient the adverse effects and inpatient stays experienced with ICE based chemotherapy. In this Phase 1 study, we planned to explore 5 dose levels of brentuximab and bendamustine: (1) Bv = 1.2mg/kg; B = 70mg/m2; (2) Bv = 1.2mg/kg; B = 80mg/m2; (3) Bv = 1.8mg/kg; B = 80mg/m2; (4) Bv = 1.8mg/kg; B = 90; and (5) Bv = 1.8mg/kg and B = 100mg/m2. Accrual followed a classic Fibonacchi dose escalation, with 3 patients being treated at each dose level. A Dose Limiting Toxicity, defined as any CTC version 4 Grade 3 or 4 toxicity, excepting modifications for neutropenia, anemia, and thrombocytopenia, nausea and vomiting, diarrhea, alopecia and fatigue, led to expansion of the dose cohort. In brief, the study population consisted of 28 patients accrued to the Phase 1 portion of the study, of which: 18 were male; 27 had HL and 1 ALCL; the median number of prior systemic therapies was 5 (range 1-14); with 17 patients having had prior ASCT and 11 prior radiation therapy. The maximum tolerated dose (MTD) was Bv = 1.8 mg/m2 and 90 mg/m2 of bendamustine. The DLT was not reached, as the study called for only 5 dose cohorts, with the highest dose cohort being defined by the MTD of the individual drugs. To date, 27 patients were evaluable for response. Two patients (7%) experienced a complete remission, and 10 had a partial remission, for an overall response rate of 44%. Ten patients had stable disease. Interestingly, among the 9 patients who had prior Bv, 4 responded (44%) (PR=4, SD=2, POD=3), and of the 4 patients who had prior B, 2 responded (50%) (PR=2, SD=1, POD=1). The study is now being expanded into a Phase 2 study, where an additional 37 patients will be accrued. In addition, plasma and serum was collected from every patient, which are being analyzed for a variety of immunological biomarkers which will be correlated with toxicity and response. We believe that in this very heavily treated patient population, the combination of Bv and B represents a highly promising combination for patients with relapsed or refractory HL and ALCL. Table Dose Cohort No. Patients Responses Complete Response Dose Cohort 1 Bv = 1.2 mg/kgB = 70 mg/m2 7 4 1 Dose Cohort 2 Bv = 1.2 mg/kgB = 80 mg/m2 3 2 0 Dose Cohort 3 Bv = 1.8 mg/kgB = 80 mg/m2 7 3 1 Dose Cohort 4 Bv = 1.8 mg/kgB = 90 mg/m2 11 3 Dose Cohort 5Bv = 1.8 mg/kgB = 100 mg/m2 *Not accrued 0 0 Total 28 (27 evaluable) 12 2 * Decision was made not to exceed the MTD of individual drugs Disclosures O'Connor: Millennium Pharmaceuticals: Consultancy; Celgene : Consultancy. Amengual:Acetylon Pharmaceuticals, INC: Research Funding.

A phase III randomized study comparing cisplatin and fluorouracil as single agents and in combination for advanced squamous cell carcinoma of the head and neck.

1992 ◽  
Vol 10 (2) ◽  
pp. 257-263 ◽  
Author(s):  
C Jacobs ◽  
G Lyman ◽  
E Velez-García ◽  
K S Sridhar ◽  
W Knight ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Response Rate ◽  
Performance Status ◽  
Randomized Study ◽  
Dose Intensity ◽  
Phase Iii ◽  
Hematologic Toxicity ◽  
Significant Difference

PURPOSE To determine whether combination chemotherapy is superior to single agents for recurrent/metastatic head and neck cancer, we compared the efficacy and toxicity of cisplatin (CP) and fluorouracil (5-FU), alone and in combination in a phase III trial. PATIENTS AND METHODS Two hundred forty-nine patients with recurrent head and neck cancer were randomized to one of three treatments: CP (100 mg/m2) and 5-FU (1 g/m2 x 4), CP, or 5-FU every 3 weeks. RESULTS The overall response rate to the combination (32%) was superior to that of CP (17%) or 5-FU (13%) (P = .035). Response was associated with good performance status (PS) but not with primary site, site of recurrence, histology, prior irradiation, or relative dose intensity. Median time to progression was less than 2.5 months, and there was no significant difference in median survival (5.7 months) among the groups. By multivariate analysis, patients with better PS and poorly differentiated tumors had superior survival. Hematologic toxicity and alopecia were worse in the combination arm. CONCLUSION Although the response rate to the combination of CP plus 5-FU was superior to that achieved with single agents, survival did not improve.

Phase II Randomized Trial of Temozolomide and Concurrent Radiotherapy in Patients With Brain Metastases

2002 ◽  
Vol 20 (17) ◽  
pp. 3644-3650 ◽  
Author(s):  
D. Antonadou ◽  
M. Paraskevaidis ◽  
G. Sarris ◽  
N. Coliarakis ◽  
I. Economou ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Randomized Trial ◽  
Response Rate ◽  
External Beam Radiotherapy ◽  
Objective Response ◽  
Complete Response ◽  
Hematologic Toxicity ◽  
Neurologic Symptom ◽  
Symptom Evaluation ◽  
Radiotherapy Alone

PURPOSE: To determine the efficacy, tolerability, and safety of concurrent temozolomide and radiotherapy in patients with previously untreated brain metastases. PATIENTS AND METHODS: Fifty-two patients with brain metastases from solid tumors were randomized to oral temozolomide (75 mg/m2/d) concurrent with 40-Gy fractionated conventional external-beam radiotherapy (2 Gy, 5 d/wk) for 4 weeks versus 40-Gy radiotherapy alone. The group receiving temozolomide and radiotherapy continued temozolomide therapy (200 mg/m2/d) for 5 days every 28 days for an additional six cycles. The primary end points were radiologic response and neurologic symptom evaluation. RESULTS: The objective response rate was significantly (P = .017) improved in patients receiving temozolomide and radiotherapy versus radiotherapy alone. Among 24 patients assessable for response in the temozolomide group, 23 (96%) of 24 responded, including nine (38%) patients with a complete response and 14 (58%) patients with a partial response. With radiotherapy alone, 14 (67%) of 21 assessable patients responded, including seven (33%) complete responses and seven (33%) partial responses. There was marked neurologic improvement in the group receiving temozolomide, and the proportion of patients requiring corticosteroids 2 months after treatment was lower in the temozolomide group compared with radiotherapy alone (67% v 91%, respectively). Daily temozolomide concurrent with radiotherapy was generally well tolerated; however, grade ≥ 2 nausea (48% v 13%, P = .13) and vomiting (32% v 0%, P = .004) were significantly increased in the temozolomide group. Hematologic toxicity was predictable and reversible. CONCLUSION: Temozolomide is safe, and a significant improvement in response rate was observed when administered in combination with radiotherapy in patients with previously untreated brain metastases. A larger randomized trial is warranted to verify these results.

Phase I study of repeated cycles of high-dose cyclophosphamide, etoposide, and cisplatin administered without bone marrow transplantation.

1990 ◽  
Vol 8 (10) ◽  
pp. 1728-1738 ◽  
Author(s):  
J A Neidhart ◽  
W Kohler ◽  
C Stidley ◽  
A Mangalik ◽  
A Plauche ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Phase I ◽  
Performance Status ◽  
Complete Response ◽  
High Dose ◽  
Hematologic Toxicity ◽  
Tumor Type ◽  
Advanced Malignancy ◽  
Prior Therapy ◽  
And Performance

Forty-two patients with advanced malignancy judged unlikely to respond to standard treatment received high-dose combination chemotherapy with cyclophosphamide, etoposide, and cisplatin in a phase I trial. Twenty-two of these patients who had at least a partial response (PR) to the first cycle of therapy received a second cycle, and eight patients received three or more cycles of therapy. Bone marrow replacement was not used. The maximum-tolerated doses (MTDs) were cyclophosphamide 2.5 g/m2 on days 1 and 2; etoposide 500 mg/m2 on days 1, 2, and 3; and cisplatin 50 mg/m2 on days 1, 2, and 3. Hematologic toxicity was not dose-limiting by study design. Recovery to an absolute granulocyte count above 100/microL occurred at a median of 9 days from onset (range, 3 to 23 days) at the MTD. Recovery was delayed after the third cycle. Only one patient on his third cycle failed to recover peripheral blood counts and died of sepsis an day 43. Hematologic toxicity was not dose-dependent. Nonhematologic toxicities included emesis, fatigue, alopecia, diarrhea, and anorexia and were generally well tolerated. The dose-limiting toxicities were fatal pulmonary or cardiac toxicities in five of nine patients treated at the highest dose level. Patients likely to do well can be selected by tumor type, response to prior therapy, and performance status. Nine of 36 assessable patients had a complete response (CR) and 13 a PR for a response rate of 61%. Five patients (12%) remain alive and free of disease at 15 to 32 months. Repeated cycles of dose-intensive combination therapy can produce long-term disease-free remissions in patients with refractory tumor types. The toxicity of the regimen is acceptable if patients are carefully selected.

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