Dacarbazine, Cisplatin, and Interferon-Alfa-2b With or Without Interleukin-2 in Metastatic Melanoma: A Randomized Phase III Trial (18951) of the European Organisation for Research and Treatment of Cancer Melanoma Group

2005 ◽  
Vol 23 (27) ◽  
pp. 6747-6755 ◽  
Author(s):  
Ulrich Keilholz ◽  
Cornelis J.A. Punt ◽  
Martin Gore ◽  
Wim Kruit ◽  
Poulam Patel ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Single Agent ◽  
Interleukin 2 ◽  
Progression Free Survival ◽  
Interferon Alfa ◽  
Phase Iii ◽  
High Dose ◽  
Phase Iii Trial ◽  
Significant Difference ◽  
To Receive

Background Based on phase II trial results, chemoimmunotherapy combinations have become the preferred treatment for patients with metastatic melanoma in many institutions. This study was performed to determine whether interleukin-2 (IL-2) as a component of chemoimmunotherapy influences survival of patients with metastatic melanoma. Patients and Methods Patients with advanced metastatic melanoma were randomly assigned to receive dacarbazine 250 mg/m2 and cisplatin 30 mg/m2 on days 1 to 3 combined with interferon-alfa-2b 10 × 106 U/m2 subcutaneously on days 1 through 5 without (arm A) or with (arm B) a high-dose intravenous decrescendo regimen of IL-2 on days 5 through 10 (18 × 106 U/m2/6 hours, 18 × 106 U/m2/12 hours, 18 × 106 U/m2/24 hours, and 4.5 × 106 U/m2 for 3 × 24 hours). Treatment cycles were repeated in the absence of disease progression every 28 days to a maximum of four cycles. Results Three hundred sixty-three patients with advanced metastatic melanoma were accrued. The median survival was 9 months in both arms, with a 2-year survival rate of 12.9% and 17.6% in arms A and B, respectively (P = .32; hazard ratio, 0.90; 95% CI, 0.72 to 1.11). There was also no statistically significant difference regarding progression-free survival (median, 3.0 v 3.9 months) and response rate (22.8% v 20.8%). Conclusion Despite its activity in melanoma as a single agent or in combination with interferon-alfa-2b, the chosen schedule of IL-2 added to the chemoimmunotherapy combination had no clinically relevant activity.

scholarly journals Phase III Trial Comparing Concurrent Biochemotherapy With Cisplatin, Vinblastine, Dacarbazine, Interleukin-2, and Interferon Alfa-2b With Cisplatin, Vinblastine, and Dacarbazine Alone in Patients With Metastatic Malignant Melanoma (E3695): A Trial Coordinated by the Eastern Cooperative Oncology Group

2008 ◽  
Vol 26 (35) ◽  
pp. 5748-5754 ◽  
Author(s):  
Michael B. Atkins ◽  
Jessie Hsu ◽  
Sandra Lee ◽  
Gary I. Cohen ◽  
Lawrence E. Flaherty ◽  
...  
Keyword(s):  
Overall Survival ◽  
Metastatic Melanoma ◽  
Interleukin 2 ◽  
Progression Free Survival ◽  
Response Rates ◽  
Interferon Alfa ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
Free Survival ◽  
Median Progression Free Survival

Purpose Phase II trials with biochemotherapy (BCT) have shown encouraging response rates in metastatic melanoma, and meta-analyses and one phase III trial have suggested a survival benefit. In an effort to determine the relative efficacy of BCT compared with chemotherapy alone, a phase III trial was performed within the United States Intergroup. Patients and Methods Patients were randomly assigned to receive cisplatin, vinblastine, and dacarbazine (CVD) either alone or concurrent with interleukin-2 and interferon alfa-2b (BCT). Treatment cycles were repeated at 21-day intervals for a maximum of four cycles. Tumor response was assessed after cycles 2 and 4, then every 3 months. Results Four hundred fifteen patients were enrolled, and 395 patients (CVD, n = 195; BCT, n = 200) were deemed eligible and assessable. The two study arms were well balanced for stratification factors and other prognostic factors. Response rate was 19.5% for BCT and 13.8% for CVD (P = .140). Median progression-free survival was significantly longer for BCT than for CVD (4.8 v 2.9 months; P = .015), although this did not translate into an advantage in either median overall survival (9.0 v 8.7 months) or the percentage of patients alive at 1 year (41% v 36.9%). More patients experienced grade 3 or worse toxic events with BCT than CVD (95% v 73%; P = .001). Conclusion Although BCT produced slightly higher response rates and longer median progression-free survival than CVD alone, this was not associated with either improved overall survival or durable responses. Considering the extra toxicity and complexity, this concurrent BCT regimen cannot be recommended for patients with metastatic melanoma.

Phase III Trial of Immunotherapy with Recombinant Interleukin-2 (rIL-2) Versus Observation in Patients < 60 Years with Acute Myeloid Leukemia (AML) in First Remission (CR1): Preliminary Results from Cancer and Leukemia Group B (CALGB) 19808.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 157-157 ◽  
Author(s):  
Jonathan E. Kolitz ◽  
Vera Hars ◽  
Daniel J. DeAngelo ◽  
Steven L. Allen ◽  
Thomas C. Shea ◽  
...  
Keyword(s):  
Survival Rate ◽  
Interleukin 2 ◽  
Cytotoxic Agents ◽  
Phase Iii ◽  
Cross Resistance ◽  
High Dose ◽  
Phase Iii Trial ◽  
Effector Cells ◽  
To Receive

Abstract The CALGB evaluated the use of rIL-2 for immunotherapy of minimal residual disease in a phase III trial in patients with AML in first CR after completing all planned chemotherapy. The rationale supporting the use of rIL-2 in this setting includes its ability to effect antigen-independent cytotoxicity against AML blasts, its non-cross resistance with cytotoxic agents, and its ability to expand cytotoxic T and natural killer (NK) cells. Pts &lt; 60 years with untreated non-M3 AML were eligible. 734 patients were enrolled. The first 302 patients were randomized between 2 induction regimens: Ara-C, Daunorubicin, and Etoposide (ADE) or ADEP with the P-glycoprotein modulator PSC-833 (Kolitz et al, ASH 2005). The remaining 432 patients received ADE induction. Post-remission therapy was based on cytogenetic risk factors: patients with Core Binding Factor (CBF) AML received 3 courses of High-Dose Ara-C (HiDAC), while all others were assigned to receive a 2 step autologous transplant (ASCT) regimen (Linker et al, Biol Blood Marrow Transpl 2000). Randomization between rIL-2 and observation was to occur no later than 120 days after day 1 of the last HiDAC cycle or day 0 of ASCT, as soon as the neutrophil count &gt; 750/μl, platelets &gt; 50,000/μl with bone marrow showing a leukemia-free state and trilineage maturation and recovery from non-hematological toxicity to &lt; grade 2. The 90 day immunotherapy regimen consisted of low-dose rIL-2 sequences for expanding cytotoxic effector cells and brief, higher dose bolus treatments aimed at activating them. rIL-2 was given SC at 1 x 106 IU/m2 on days 1–14, 19–28, 33–42, 47–56, 61–70 and 75–90, and 12–15 x 106 IU/m2 on days 15–17, 29–31, 43–45, 57–59 and 71–73. CR was achieved in 77% of evaluable patients. After HiDAC consolidation or ASCT, patient refusal, early relapse, and delayed blood count recovery accounted for nearly all failures to undergo randomization to IL-2 or observation. The distribution of patients with CBF and non-CBF AML was comparable between the randomized arms. The median follow-up time from the post-remission randomization date for the surviving patients is 29 months. By intention-to-treat, for the 214 randomized patients, the 3-year disease-free survival rate is 45% (95% CI: 35%, 56%) on the observation arm and 56% (47%, 67%) on the rIL-2 arm (p=0.11; logrank test); the 3-year overall survival rate is 61% (52%, 72%) for patients randomized to observation and 68% (58%, 79%) for the rIL-2 arm (p=.0.09). Twenty-nine of the 107 patients randomized to rIL-2 therapy either refused to receive rIL-2 or were unable to start because of unresolved toxicities; another 28 patients started treatment but failed to complete their 90-day course. Grade 4 toxicities were neutropenia (17%), thrombocytopenia (11%), febrile neutropenia (FN, 1%), increased bilirubin (1%) and hypocalcemia (1%). Grade 3 toxicities, observed in 10%–14% of patients, were hypotension, fatigue, dehydration and FN. We conclude that post-consolidation immunotherapy with 90 days of rIL-2 is tolerable but not well accepted by patients and/or physicians. Further follow-up and additional analyses are planned, correlating outcomes with clinical subsets, amount of rIL-2 therapy received, as well as measurements of ex vivo cytotoxicity mediated by patients’ effector cells against cryopreserved autologous AML blasts.

scholarly journals Interferon alfa-2a and interleukin-2 with or without cisplatin in metastatic melanoma: a randomized trial of the European Organization for Research and Treatment of Cancer Melanoma Cooperative Group.

1997 ◽  
Vol 15 (7) ◽  
pp. 2579-2588 ◽  
Author(s):  
U Keilholz ◽  
S H Goey ◽  
C J Punt ◽  
T M Proebstle ◽  
R Salzmann ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Response Rate ◽  
Interleukin 2 ◽  
Progression Free Survival ◽  
Interferon Alfa ◽  
Survival Duration ◽  
High Dose ◽  
Free Survival ◽  
Ifn Alpha ◽  
Cytokine Treatment

PURPOSE The combination of interferon alfa-2a (IFN alpha) and high-dose interleukin-2 (IL-2) is active in metastatic melanoma. The addition of cisplatin (CDDP) has resulted in response rates greater than 50%. This study was performed to determine whether the addition of CDDP to a cytokine treatment regimen with IFN alpha and high-dose IL-2 influences survival of patients with metastatic melanoma. PATIENTS AND METHODS Patients with advanced metastatic melanoma were randomly assigned to receive treatment with IFN alpha 10 x 10(6) U/m2 subcutaneously on days 1 through 5 and a high-dose intravenous decrescendo regimen of IL-2 on days 3 through 8 (18 mIU/ m2/6 hours, 18 mIU/m2/12 hours, 18 mIU/m2/24 hours, and 4.5 mIU/m2/24 hours x 3) without (arm A) or with (arm B) CDDP 100 mg/m2 on day 1. Treatment cycles were repeated every 28 days to a maximum of four cycles. RESULTS One hundred thirty-eight patients with advanced metastatic melanoma, of whom 87% had visceral metastases, were accrued for the trial. Both regimens were feasible in a multicenter setting. The objective response rate was 18% without and 33% with CDDP (P = .04). The progression-free survival was 53 days without and 92 days with CDDP (P = .02, Wilcoxon; P = .09, log-rank). There was no statistically significant difference in survival between treatment arms, with a median overall survival duration for all patients of 9 months. CONCLUSION The addition of CDDP to cytokine treatment with IFN alpha and IL-2 does not influence survival of patients with advanced metastatic melanoma, despite a significant increase in response rate and progression-free survival.

Sequential Biochemotherapy Versus Chemotherapy for Metastatic Melanoma: Results From a Phase III Randomized Trial

2002 ◽  
Vol 20 (8) ◽  
pp. 2045-2052 ◽  
Author(s):  
Omar Eton ◽  
Sewa S. Legha ◽  
Agop Y. Bedikian ◽  
J. Jack Lee ◽  
Antonio C. Buzaid ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Metastatic Melanoma ◽  
Multivariate Analyses ◽  
Interleukin 2 ◽  
Therapy Response ◽  
Interferon Alfa ◽  
Phase Iii ◽  
Time To Progression ◽  
Phase Iii Trial ◽  
Melanoma Patients

PURPOSE: The addition of cytokines to chemotherapy has produced encouraging results in advanced melanoma. In this phase III trial, we compared the effects of chemotherapy (cisplatin, vinblastine, and dacarbazine [CVD]) with those of sequential biochemotherapy consisting of CVD plus interleukin-2 and interferon alfa-2b. PATIENTS AND METHODS: Metastatic melanoma patients who had not previously received chemotherapy were stratified by prognostic factors and given chemotherapy or biochemotherapy. CVD consisted of dacarbazine (days 1 and 22) and cisplatin and vinblastine (days 1 to 4 and 22 to 25). Biochemotherapy involved CVD with vinblastine reduced 25% plus interleukin-2 by 24-hour continuous infusion (on days 5 to 8, 17 to 20, and 26 to 29) and interferon alfa-2b by subcutaneous injection (on days 5 to 9, 17 to 21, and 26 to 30). Response was assessed every 6 weeks. RESULTS: Among 190 patients enrolled, 91 were assessable for biochemotherapy and 92 for chemotherapy. Ten percent of the patients were alive a median of 52 months from start of therapy. Response rates were 48% for biochemotherapy and 25% for chemotherapy (P = .001); six patients given biochemotherapy and two given chemotherapy had complete responses. Median time to progression (TTP) was 4.9 months for biochemotherapy and 2.4 months for chemotherapy (P = .008); median survival was 11.9 and 9.2 months, respectively (P = .06). The influence of treatment on TTP and survival was confirmed in multivariate analyses with other prognostic factors not included in the original stratification. Biochemotherapy produced substantially more constitutional, hemodynamic, and myelosuppressive toxic effects. CONCLUSION: Cytokines substantially augment the antitumor activity of chemotherapy at the expense of considerable toxicity in patients with metastatic melanoma.

Phase III Trial in Metastatic Gastroesophageal Adenocarcinoma with Fluorouracil, Leucovorin Plus Either Oxaliplatin or Cisplatin: A Study of the Arbeitsgemeinschaft Internistische Onkologie

2008 ◽  
Vol 26 (9) ◽  
pp. 1435-1442 ◽  
Author(s):  
Salah-Eddin Al-Batran ◽  
Joerg Thomas Hartmann ◽  
Stephan Probst ◽  
Harald Schmalenberg ◽  
Stephan Hollerbach ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Phase Iii ◽  
Serious Adverse Events ◽  
Phase Iii Trial ◽  
Free Survival ◽  
Significant Difference ◽  
Time To Treatment Failure ◽  
Gastroesophageal Adenocarcinoma ◽  
Reduced Toxicity ◽  
To Receive

Purpose This study was designed to compare fluorouracil, leucovorin, and oxaliplatin with fluorouracil, leucovorin, and cisplatin in patients with advanced gastric cancer. Patients and Methods Patients with previously untreated advanced adenocarcinoma of the stomach or esophagogastric junction were randomly assigned to receive either fluorouracil 2,600 mg/m2 via 24-hour infusion, leucovorin 200 mg/m2, and oxaliplatin 85 mg/m2 (FLO) every 2 weeks or fluorouracil 2,000 mg/m2 via 24-hour infusion, leucovorin 200 mg/m2 weekly, and cisplatin 50 mg/m2 every 2 weeks (FLP). The primary end point was progression-free survival (PFS). Results Two hundred twenty patients (median age, 64 years; metastatic, 94%) were randomly assigned. FLO was associated with significantly less (any grade) anemia (54% v 72%), nausea (53% v 70%), vomiting (31% v 52%), alopecia (22% v 39%), fatigue (19% v 34%), renal toxicity (11% v 34%), thromboembolic events (0.9% v 7.8%), and serious adverse events related to the treatment (9% v 19%). FLP was associated with significantly less peripheral neuropathy (22% v 63%). There was a trend toward improved median PFS with FLO versus FLP (5.8 v 3.9 months, respectively; P = .077) and no significant difference in median overall survival (10.7 v 8.8 months, respectively). However, in patients older than 65 years (n = 94), treatment with FLO resulted in significantly superior response rates (41.3% v 16.7%; P = .012), time to treatment failure (5.4 v 2.3 months; P < .001), and PFS (6.0 v 3.1 month; P = .029) and an improved OS (13.9 v 7.2 months) as compared with FLP, respectively. Conclusion FLO reduced toxicity as compared with FLP. In older adult patients, FLO also seemed to be associated with improved efficacy.

Assessment of absolute lymphocyte count (ALC) as a predictor of progression-free survival (PFS) and overall response rate (ORR) in metastatic melanoma (MM) patients (pts) treated with high-dose interleukin-2 (HD IL-2).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 9096-9096
Author(s):  
Jeffrey Thomas Yorio ◽  
Patricia S Fox ◽  
Richard Wayne Joseph ◽  
Roland Bassett ◽  
Michael A. Davies
Keyword(s):  
Metastatic Melanoma ◽  
Clinical Benefit ◽  
Hematological Parameters ◽  
Interleukin 2 ◽  
Progression Free Survival ◽  
Absolute Lymphocyte Count ◽  
Cancer Center ◽  
High Dose ◽  
Continuous Variables ◽  
Significant Difference

9096 Background: HD IL-2 is an approved immunotherapy that can achieve durable cures in MM pts. Due to toxicity and low ORR, identification of predictors of clinical benefit would enhance pt selection and outcomes with HD IL-2. Recent research identified a positive correlation for ALC ≥ 1000 (either at baseline or at dose 3) with OS among MM pts treated with the immunotherapy agent ipilimumab. We tested the hypothesis that ALC (≥ 1000) or other hematological parameters correlates with clinical benefit from HD IL2. Methods: Results of hematologic testing in patients (n=98) treated with HD IL2 at MD Anderson Cancer Center were collected, including absolute levels of neutrophils (ANC), lymphocytes (ALC), monocytes (AMC), eosinophils (AEC), and platelets (APC) at baseline, after cycle 1 (C1), and after cycle 2 (C2) of HD IL-2; changes in each parameter for each interval were also calculated. Hematologic values were assessed as categorical (for ALC, ≥ 1000 Yes/No; other parameters, above upper limit of normal [ULN] Yes/No) and continuous variables. Associations between these parameters and PFS and ORR were analyzed. Results: ALC was≥ 1000 in 75 pts (76%) at baseline, in 81 (83%) after C1, and in 80 of 86 pts (93%) after completion of C2 of HD IL-2. PFS was not significantly associated with ALC ≥ 1000 at baseline (HR 0.69, p=0.13), after C1 (HR 1.32, p=0.33), or after C2 (HR 1.01, p=0.98). ALC ≥ 1000 at each timepoint was not significantly associated with ORR or OS. There was no significant difference in the change in ALC with HD IL2 treatment among responders versus non-responders. Among baseline hematological factors, APC > ULN was significantly associated with PFS (p=0.001), but it was rare (2/98 patients). Exploratory analyses identified significantly shorter PFS for patients with baseline APC > 300 (11%, HR 2.75, p=0.002). Analysis of hematologic factors as continuous values identified significant associations with PFS for AMC (HR 2.42, p=0.03) and AEC (HR 1.73, p=0.009) after C2. Conclusions: ALC ≥ 1000 did not correlate with PFS, ORR, or OS with HD IL-2 therapy in this cohort of metastatic melanoma pts.

scholarly journals Role of Immunotherapy for Renal Cell Cancer in 2011

2011 ◽  
Vol 9 (9) ◽  
pp. 1011-1018 ◽  
Author(s):  
Saby George ◽  
Roberto Pili ◽  
Michael A. Carducci ◽  
Jenny J. Kim
Keyword(s):  
Renal Cell ◽  
Checkpoint Inhibitors ◽  
Cell Cancer ◽  
Single Agent ◽  
Mammalian Target Of Rapamycin ◽  
Interleukin 2 ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Current Status ◽  
High Dose

High-dose interleukin-2 (IL-2) and interferon were the most commonly administered therapies before the recent introduction of targeted agents, including vascular endothelial growth factor and mammalian target of rapamycin pathway inhibitors. Although the new agents result in a progression-free survival benefit, high-dose IL-2 remains the only agent with proven efficacy in producing durable complete and partial responses in patients with metastatic renal cell carcinoma (RCC). Furthermore, although the use of single-agent interferon has decreased significantly since the introduction of targeted therapy, it remains in the frontline setting in combination with bevacizumab as a result of 2 large phase III trials. Lastly, improved understanding of immune regulation has led to the advancement of targeted immunotherapy using immune checkpoint inhibitors that have shown promising activity and are moving forward in clinical development. This article focuses on the current status of immunotherapy in the management of metastatic RCC.

Randomized phase III trial of treatment with high-dose interleukin-2 either alone or in combination with interferon alfa-2a in patients with advanced melanoma.

1993 ◽  
Vol 11 (10) ◽  
pp. 1969-1977 ◽  
Author(s):  
J A Sparano ◽  
R I Fisher ◽  
M Sunderland ◽  
K Margolin ◽  
M L Ernest ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Interim Analysis ◽  
Response Rate ◽  
Interleukin 2 ◽  
Advanced Melanoma ◽  
Interferon Alfa ◽  
Phase Iii ◽  
High Dose ◽  
Phase Iii Trial ◽  
Ifn Alpha

PURPOSE To compare the response rate, survival, and toxicity of treatment with high-dose intravenous (IV) bolus interleukin-2 (IL-2) plus interferon alfa-2a (IFN-alpha) with high-dose IL-2 alone in patients with advanced melanoma in a randomized phase III trial design. PATIENTS AND METHODS Eighty-five patients with advanced melanoma were randomly assigned to receive IL-2 6 X 10(6) U/m2 per dose every 8 hours as tolerated for a maximum of 14 doses on days 1 through 5 and 15 through 19, or IL-2 4.5 X 10(6) U/m2 per dose, plus IFN-alpha 3 X 10(6) U/m2 using an identical schedule. A planned interim analysis was performed after 85 patients were entered, which forms the basis for this report. RESULTS Partial response (PR) occurred in two of 44 patients (5%; 95% confidence interval, 1% to 15%) receiving IL-2 alone, compared with four of 41 patients (10%; 95% confidence interval, 3% to 23%) receiving IL-2/IFN-alpha (P = .30). There were no complete responses (CRs). The median duration of response was 11.5 months (range, 2.0 to 15.7+). There was no significant difference in the median survival duration for patients receiving IL-2 alone (10.2 months) compared with patients receiving IL-2/IFN-alpha (9.7 months). The median and mean number of doses of IL-2 were equivalent in both groups, as was toxicity. There were three treatment-related deaths, two in the IL-2-alone arm and one in the IL-2/IFN-alpha arm. The trial was terminated after the first interim analysis based on predefined early-stopping rules, which included termination if the response rate in the IL-2/IFN-alpha arm was less than 25%. CONCLUSION Using the preparation, dose, and schedule of IL-2 in our trial, IFN-alpha failed to enhance significantly the response rate to high-dose IL-2 in the treatment of patients with advanced melanoma.

scholarly journals Long-term progression-free survival of patients with metastatic melanoma or renal cell carcinoma following high-dose interleukin-2

2021 ◽  
Vol 69 (4) ◽  
pp. 888-892
Author(s):  
Joseph I Clark ◽  
Brendan Curti ◽  
Elizabeth J Davis ◽  
Howard Kaufman ◽  
Asim Amin ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Melanoma ◽  
Systemic Therapy ◽  
Renal Cell ◽  
Interleukin 2 ◽  
Progression Free Survival ◽  
High Dose ◽  
Free Survival

High-dose interleukin-2 (HD IL-2) was approved in the 1990s after demonstrating durable complete responses (CRs) in some patients with metastatic melanoma (mM) and metastatic renal cell carcinoma (mRCC). Patients who achieve this level of disease control have also demonstrated improved survival compared with patients who progress, but limited data are available describing the long-term course. The aim of this study was to better characterize long-term survival following successful HD IL-2 treatment in patients with no subsequent systemic therapy. Eleven HD IL-2 treatment centers identified patients with survival ≥5 years after HD IL-2, with no subsequent systemic therapy. Survival was evaluated from the date of IL-2 treatment to June 2017. Treatment courses consisted of 2 1-week cycles of HD IL-2. Patients were treated with HD IL-2 alone, or HD IL-2 followed by local therapy to achieve maximal response. 100 patients are reported: 54 patients with mM and 46 patients with mRCC. Progression-free survival (PFS) after HD IL-2 ranges from 5+ years to 30+ years, with a median follow-up of 10+ years. 27 mRCC and 32 mM are alive ≥10 years after IL-2. Thus, a small subset of patients with mM and mRCC achieve long-term PFS (≥5 years) after treatment with HD IL-2 as their only systemic therapy. The ability of HD IL-2 therapy to induce prolonged PFS should be a major consideration in studies of new immunotherapy combinations for mM and mRCC.

Randomized Phase III Trial of Gemcitabine Compared With Pegylated Liposomal Doxorubicin in Patients With Platinum-Resistant Ovarian Cancer

2007 ◽  
Vol 25 (19) ◽  
pp. 2811-2818 ◽  
Author(s):  
David G. Mutch ◽  
Mauro Orlando ◽  
Tiana Goss ◽  
Michael G. Teneriello ◽  
Alan N. Gordon ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Liposomal Doxorubicin ◽  
Single Agent ◽  
Pegylated Liposomal Doxorubicin ◽  
Progression Free Survival ◽  
Therapeutic Index ◽  
Phase Iii ◽  
End Points ◽  
Platinum Resistant ◽  
Significant Difference

Purpose Ovarian cancer (OC) patients experiencing progressive disease (PD) within 6 months of platinum-based therapy in the primary setting are considered platinum resistant (Pt-R). Currently, pegylated liposomal doxorubicin (PLD) is a standard of care for treatment of recurrent Pt-R disease. On the basis of promising phase II results, gemcitabine was compared with PLD for efficacy and safety in taxane-pretreated Pt-R OC patients. Patients and Methods Patients (n = 195) with Pt-R OC were randomly assigned to either gemcitabine 1,000 mg/m2 (days 1 and 8; every 21 days) or PLD 50 mg/m2 (day 1; every 28 days) until PD or undue toxicity. Optional cross-over therapy was allowed at PD or at withdrawal because of toxicity. Primary end point was progression-free survival (PFS). Additional end points included tumor response, time to treatment failure, survival, and quality of life. Results In the gemcitabine and PLD groups, median PFS was 3.6 v 3.1 months; median overall survival was 12.7 v 13.5 months; overall response rate (ORR) was 6.1% v 8.3%; and in the subset of patients with measurable disease, ORR was 9.2% v 11.7%, respectively. None of the efficacy end points showed a statistically significant difference between treatment groups. The PLD group experienced significantly more hand-foot syndrome and mucositis; the gemcitabine group experienced significantly more constipation, nausea/vomiting, fatigue, and neutropenia but not febrile neutropenia. Conclusion Although this was not designed as an equivalency study, gemcitabine and PLD seem to have a comparable therapeutic index in this population of Pt-R taxane-pretreated OC patients. Single-agent gemcitabine may be an acceptable alternative to PLD for patients with Pt-R OC.

Sign in / Sign up

Export Citation Format

Share Document