Outpatient Biochemotherapy With Interleukin-2 and Interferon Alfa-2b in Patients With Metastatic Malignant Melanoma: Results of Two Phase II Cytokine Working Group Trials

2001 ◽  
Vol 19 (13) ◽  
pp. 3194-3202 ◽  
Author(s):  
L. E. Flaherty ◽  
M. Atkins ◽  
J. Sosman ◽  
G. Weiss ◽  
J. I. Clark ◽  
...  
Keyword(s):  
Malignant Melanoma ◽  
Antitumor Activity ◽  
Phase Ii ◽  
Working Group ◽  
Objective Response ◽  
Interleukin 2 ◽  
Metastatic Malignant Melanoma ◽  
Phase Iii ◽  
Group 2 ◽  
Group 1

PURPOSE: The Cytokine Working Group performed a randomized phase II trial of two outpatient biochemotherapy regimens to identify an outpatient regimen with high antitumor activity and less toxicity than inpatient regimens which might be compared with chemotherapy or inpatient biochemotherapy regimens in future phase III trials. PATIENTS AND METHODS: Eighty-one patients with metastatic malignant melanoma received dacarbazine 250 mg/m2/d intravenously (IV) and cisplatin 25 mg/m2/d IV on days 1, 2, and 3, plus interferon (IFN) alfa-2b 5 mU/m2 subcutaneously (SC) on days 6, 8, 10, 13, and 15, given every 28 days. Interleukin-2 (IL-2) was given daily on days 6 to 10 and 13 to 15. In group 1, IV IL-2 was given at 18.0 MU/m2, and in group 2, SC IL-2 was given at 5.0 mU/m2. RESULTS: In group 1 (IV IL-2), there were five complete responses (CRs) and 11 partial responses (PRs) among 44 patients (objective response rate [ORR], 36%; 95% confidence interval [CI], 22% to 51%). In group 2 (SC IL-2), there was one CR and five PRs among the 36 patients (ORR, 17%; 95% CI, 4% to 29%). The median survival was 10.7 months in group 1 and 7.3 months in group 2. Eleven patients in group 1 and four patients in group 2 remain alive as of the last follow-up. Toxicities in both groups were similar. No patient required hospitalization for neutropenic fever. CONCLUSION: Biochemotherapy has activity in these outpatient regimens with acceptable toxicity. The antitumor activity observed with the IV IL-2 regimen seems similar to that of inpatient biochemotherapy regimens. If inpatient biochemotherapy regimens develop an established role in the management of melanoma, future phase III trial comparisons with this outpatient IV IL-2 regimen would be appropriate.

Phase II trial of chemotherapy with high-dose FOLFIRI plus bevacizumab in the front-line treatment of patients with metastatic colorectal cancer (mCRC) and genotype UGT1A1*1/ UGT1A1*1 or UGT1A1*1/ UGT1A1*28 (FFCD 0504 trial). Results of a planned interim analysis

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4065-4065
Author(s):  
E. Mitry ◽  
O. Bouché ◽  
L. Dahan ◽  
F. Bonnetain ◽  
P. Laurent-Puig ◽  
...  
Keyword(s):  
Febrile Neutropenia ◽  
Phase Ii ◽  
Interim Analysis ◽  
Phase Ii Trial ◽  
Objective Response ◽  
High Dose ◽  
Severe Toxicity ◽  
Group 2 ◽  
Group 1

4065 Background: The antitumor efficacy of irinotecan may be dose dependent. In a recent phase II trial, the combination of high-dose irinotecan (260 mg/m2) with LV5FU2 regimen was feasible with an acceptable safety profile and promising efficacy data (Ducreux et al. Oncology 2008;74:17–24). The aim of this study was to evaluate the association of the high-dose FOLFIRI plus bevacizumab in patients (pts) selected on the UGT1A1 polymorphism, which could be predictive of the irinotecan toxicity. Methods: Pts with UGT1A1 *1/*1 (group 1) or *1/*28 (group 2) genotypes and previously untreated mCRC were treated with bevacizumab 5 mg/kg D1, irinotecan 260 mg/m2 D1, LV 400 mg/m2 D1, 5FU 400 mg/m2 IV bolus D1 and 5FU 2400 mg/m2 46h infusion D1–2 every 2 weeks. Using Bryant & Day design with OR (independent review, H0 ≤ 40%; H1 : ≥ 60%) and toxicity (gr 4 neutropenia or febrile neutropenia or gr3–4 diarrhea; H0 ≥ 20%; H1≤ 5% ) as primary endpoints; a total of 108 pts, 54 in each group, was required (alpha 5% and power 80%) with a planned interim analysis after the inclusion of 17 pts by group. The trial will be stopped at interim analysis if ≤ 7 pts had an OR and/or ≥ 3 pts had a severe toxicity. All analyses were performed in ITT. Results: At the time of interim analysis, done for group 1 when the 17th pt had a 6-months follow-up, 96 pts have been included (group 1: 40 pts, group 2: 46 pts). An objective response rate was observed in 9/17 pts but 7/17 pts had a severe toxicity (gr 4 neutropenia: 2 pts, febrile neutropenia: 2 pts, gr 3 diarrhea: 4 pts). Overall, 14/17 pts had a gr3–4 toxicity. There was no toxic death. According to interim analysis rules, the trial was closed to inclusion (for both groups) on December 16th 2008 for toxicity. The interim analysis for pts of group 2 is planned for February 2009 when the 17th patient will have a 6-months follow- up. Conclusions: High-dose FOLFIRI plus bevacizumab, although effective, was associated with a high toxicity rate among pts with UGT1A1 *1/*1 genotype. Complete tolerance, efficacy and survival results for all included patients will be presented at the meeting. [Table: see text]

Combination Chemotherapy with 1-Methyl-1-Nitrosourea and Cyclophosphamide in Metastatic Melanoma

1978 ◽  
Vol 64 (1) ◽  
pp. 89-94 ◽  
Author(s):  
Krsto Kolarić ◽  
Anton Roth ◽  
Vera Fuss
Keyword(s):  
Body Weight ◽  
Malignant Melanoma ◽  
Antitumor Activity ◽  
Lymph Nodes ◽  
Metastatic Melanoma ◽  
Combination Chemotherapy ◽  
Tumor Regression ◽  
Objective Response ◽  
Metastatic Malignant Melanoma ◽  
Melanoma Metastasis

Twenty one patients with advanced metastatic melanoma were treated with a combination of 1-methyl-1-nitrosourea (MNU) and cyclophosphamide. AH the patients had not previously been treated with cytostatics. MNU in the dose of 4 mg/kg and cyclophosphamide in the dose of 8 mg/kg body weight was administered daily. The drugs were given in 6 day cycles. Objective response (> 50% tumor regression) was obtained in 8 (38%) of the 21 treated patients, with 2 complete and 6 partial remissions. The duration of remission was 2–12 months (M = 6.2 months). Injections of MNU caused nausea and vomiting in approximately all the treated patients. Combination of these drugs, however, produced myelodepression in 33% of treated patients. This combination of drugs showed antitumor activity in metastatic malignant melanoma, particularly in melanoma metastasis of the lung, brain and lymph nodes and needs further investigation.

scholarly journals Efficacy and safety of apatinib in patients with recurrent or refractory melanoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e22026-e22026
Author(s):  
Zibing Wang ◽  
Shumin Yuan ◽  
Xiaojie Zhang ◽  
Hao Huang ◽  
Quanli Gao
Keyword(s):  
Malignant Melanoma ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Angiogenesis Inhibitor ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Metastatic Malignant Melanoma ◽  
Advanced Melanoma

e22026 Background: The prognosis of patients with metastatic malignant melanoma is very poor, a fact that is partly due to its high resistance to conventional chemotherapies. The objectives of this phase II trial were to assess the activity and tolerability of apatinib, an oral small molecule anti-angiogenesis inhibitor, in patients with recurrent advanced melanoma. Methods: This was a single arm, single center phase II trial. The primary endpoint was progression free survival (PFS), and the second endpoints was objective response rate (ORR), disease control rate (DCR) and overall survival (OS). Eligible patients received at least one prior line of therapy for advanced melanoma and experienced recurrence. Apatinib was given daily at a dose of 500 mg orally. This study was registered at ClinicalTrials.gov , number NCT03383237 . Results: A total of 17 patients were included in the final analysis. The median PFS was 4.5 months. There were two major objective responses, for a response rate of 11.8%. Thirteen patients had a stable disease, for a DCR of 88.2%. The median OS was 11.5 months. The most common clinically significant grade 3 or 4 toxicities included hypertension (n = 1) and canker sore (n = 1). No treatment-related death occurred. Conclusions: Apatinib showed antitumor activity as a second or above line therapy in patients with malignant melanoma. The toxicity was manageable. Clinical trial information: NCT03383237.

Multicentric phase II trial of gemcitabine plus capecitabine combination in the treatment of previously anthracycline(An)-treated metastatic breast cancer (MBC): SOLTI 0301 study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1051-1051 ◽  
Author(s):  
E. M. Ciruelos ◽  
J. Baselga ◽  
H. Cortes-Funes ◽  
A. Lluch ◽  
J. I. Mayordomo ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Metastatic Breast ◽  
Hematological Toxicity ◽  
Clinical Activity ◽  
Her2 Overexpression ◽  
Group 2 ◽  
Grade 3 ◽  
Group 1

1051 Background: Based on clinical activity of capecitabine(C) and gemcitabine (G) on the treatment of MBC, we performed a multicentric phase II trial of the combination to test its efficacy and safety profile. Methods: Sample size of 72 evaluable MBC patients (pts) previously An-treated (neoadjuvant 8%, adjuvant 69%, advanced 30%). Median age: 59 years (35–76 years). Estrogen Receptor positive: 47 (65%). HER2 overexpression: 16 (22%). Prior hormonal/trastuzumab allowed. Soft tissue/ganglionar/pleural/bone disease: 19 (26%); visceral metastasis: 53(74%). Stratification: previous chemotherapy (CT) for advanced disease (none: group 1; any: group 2). Study treatment: oral bid C 1,660 mg/m2/day (d) (d1–14) + iv G 1,000 mg/m2/d (d1&8). Cycles repeated every 3 weeks. RECIST/NCI-CTC 2.0 criteria. Primary end point: Objective Response Rate. Results: Response Rates and Clinical Benefit (CB) are detailed in the table . Median follow-up 7.2 months (m) (0.2–18.4). Median time to progression 11.2 m: group 1, 12 m (95%CI: 6.4–14.5); group 2, 8.9 m (95%CI: 6.9–14).Total and median administered cycles/pt: 479 and 8. Delayed cycles: 103(21.5%): 27% due to hematological toxicity, 11% due to non-hematological toxicity, 62% due to other causes. C dose reduced in 27 cycles (5.6%), 12 of them due to non- hematological toxicity. G dose reduced in 169 cycles (35%), mostly on day 8, and due to hematological toxicity (80% of reduced cycles). Grade 3–4 neutropenia: 32 pts (56%), 1 case of febrile neutropenia. Grade 3–4 non-hematological toxicities: asthenia 8 pts (14%), hand- foot syndrome 6 pts (10.5%), mucositis 3 pts (5%), diarrhea 2 pts (3.5%). Conclusions: Combination of C+G in the treatment of previously anthracycline-treated MBC is safe and active, with a manageable toxicity profile and a good clinical activity. [Table: see text] No significant financial relationships to disclose.

Safety of Treatment of Metastatic Breast Cancer With Trastuzumab Beyond Disease Progression

2004 ◽  
Vol 22 (6) ◽  
pp. 1063-1070 ◽  
Author(s):  
Debu Tripathy ◽  
Dennis J. Slamon ◽  
Melody Cobleigh ◽  
Andrew Arnold ◽  
Mansoor Saleh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Disease Progression ◽  
Cardiac Dysfunction ◽  
Objective Response ◽  
Metastatic Breast ◽  
Phase Iii ◽  
Extension Study ◽  
Group 2 ◽  
Group 1

Purpose In a pivotal phase III trial, the addition of trastuzumab to chemotherapy significantly improved response rate, time to disease progression, and overall survival in women with HER2 overexpressing metastatic breast cancer. We conducted an extension study to this trial to obtain additional safety information and to provide trastuzumab following disease progression. Patients and Methods A total of 247 patients with documented disease progression received weekly intravenous trastuzumab in the extension study. Concurrent therapies were administered at the discretion of the treating physician. Patient groups were based on initial study treatment: chemotherapy alone (group 1, n = 154) or chemotherapy plus trastuzumab (group 2, n = 93). Results Sixty-eight percent of group 1 and 76% of group 2 received chemotherapy plus trastuzumab in the extension trial; the remainder received trastuzumab alone or combined with palliative radiotherapy or hormonal therapy. Seventy-six percent of group 1 and 55% of group 2 experienced at least one adverse event, similar to effects observed in the pivotal trial. Symptomatic or asymptomatic cardiac dysfunction occurred in 9% of group 1 and 2% of group 2 patients. Overall objective response rates were 14% in group 1 and 11% in group 2; median durations of response exceeded 6 months in both groups. Conclusion Our results suggest that prolonged use of trastuzumab therapy is safe and well tolerated. Longer durations of therapy did not appear to increase the risk of cardiac dysfunction. Patients progressing on trastuzumab-containing therapy demonstrate some response to a second trastuzumab-containing regimen. The independent contribution of trastuzumab in this setting merits further study.

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