Multiinstitutional phase II trial of intensive combination chemoimmunotherapy for metastatic melanoma.

PURPOSE To evaluate the activity and toxicity of combined high-dose cisplatin, dacarbazine (DTIC), and tamoxifen chemotherapy and high-dose bolus interleukin-2 (IL-2) in patients with metastatic melanoma. PATIENTS AND METHODS Patients with metastatic melanoma, Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and normal organ function were enrolled onto this multiinstitutional Cytokine Working Group trial. Patients received intensive chemoimmunotherapy consisting of cisplatin (50 mg/m2) and DTIC (350 mg/m2) intravenously (IV) on days 1 to 3 and 43 to 45, IL-2 600,000 IU/kg IV every 8 hours on days 12 to 16 and 26 to 30 (maximum, 28 doses), and tamoxifen 20 mg orally each day. Patients were evaluated for response at day 63 of each cycle, and responding patients were given a second cycle of therapy beginning on day 71 to 85. RESULTS Thirty-eight patients were entered onto this study. Toxicities were as expected for the chemotherapy and immunotherapy components of this regimen. Overlapping toxicity consisted primarily of thrombocytopenia (76% of patients required platelet transfusions), neutropenia, anemia, fatigue, and weight loss. Despite these cytopenias, bleeding and infectious complications were rare. There were no treatment-related deaths. Three patients achieved a complete response (CR; 8%), and 13 achieved a partial response (PR). The overall objective response rate was 42% (95% confidence interval [CI], 26% to 58%). Six additional patients had greater than 50% tumor reduction at day 63, which did not persist until a subsequent evaluation. The median duration of response was 5 months (range, 2 to 20+), and the median survival duration was 11 months. CONCLUSION This intensive treatment regimen appears to possess activity in metastatic melanoma comparable, but not superior, to that of other less intensive cisplatin- and IL-2-based chemoimmunotherapy regimens. Although the toxicity and complexity of this regimen make it unsuitable for phase III testing and impractical for more widespread use, the results of this study support a potential favorable interaction between IL-2 and chemotherapy in this disease and highlight the need for appropriately designed phase III trials.

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Paclitaxel for platinum-refractory ovarian cancer: results from the first 1,000 patients registered to National Cancer Institute Treatment Referral Center 9103.

Journal of Clinical Oncology ◽

10.1200/jco.1993.11.12.2405 ◽

1993 ◽

Vol 11 (12) ◽

pp. 2405-2410 ◽

Cited By ~ 182

Author(s):

E L Trimble ◽

J D Adams ◽

D Vena ◽

M J Hawkins ◽

M A Friedman ◽

...

Keyword(s):

Ovarian Cancer ◽

Performance Status ◽

Objective Response ◽

Eastern Cooperative Oncology Group ◽

Complete Response ◽

Survival Duration ◽

Investigational Drug ◽

Ecog Performance Status ◽

Platinum Refractory ◽

Grade 3

PURPOSE To provide an investigational drug, paclitaxel, now commercially available, to women with refractory ovarian cancer and to evaluate response and toxicity in these patients. PATIENTS AND METHODS Patients with platinum-refractory ovarian cancer, Eastern Cooperative Oncology Group (ECOG) performance status 0 to 3, at least three prior chemotherapy regimens, adequate hepatic and renal function, and no significant cardiac history were eligible. Patients were treated with paclitaxel 135 mg/m2 administered by 24-hour continuous intravenous infusion every 3 weeks. RESULTS Leukopenia was the most frequent toxicity, with 78% of patients experiencing grade 3 or 4 toxicity. Other grade 3 and 4 toxicities were less common: fever (33%), infection (12%), thrombocytopenia (8%), vomiting (7%), cardiac (2%), neurologic (2%), and mucositis (1%). Fifteen treatment-related deaths (1.5%) were reported. The objective response rate was 22% (4% complete response [CR], 18% partial response; 95% confidence interval [CI] for overall response, 19% to 25%). The median time to progression from treatment initiation was 7.1 months in responding patients and 4.5 months for all patients. The median survival duration was 8.8 months. CONCLUSION Paclitaxel has shown activity in women with platinum-refractory ovarian cancer, and it can be administered with an acceptable safety profile. Further research is needed to determine the optimal role of paclitaxel in the primary and salvage treatment of ovarian cancer.

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ECOG Performance Status Affects Efficacy, but Not Safety, of Lenalidomide/Dexamethasone in Relapsed/Refractory Multiple Myeloma (MM009/010 Sub-Analysis).

Blood ◽

10.1182/blood.v110.11.2721.2721 ◽

2007 ◽

Vol 110 (11) ◽

pp. 2721-2721

Author(s):

Asher A. Chanan-Khan ◽

Meletios Dimopoulos ◽

Donna Weber ◽

Marta Olesnyckyj ◽

Zhinuan Yu ◽

...

Keyword(s):

Multiple Myeloma ◽

Clinical Response ◽

Therapeutic Option ◽

Performance Status ◽

Eastern Cooperative Oncology Group ◽

Complete Response ◽

Response To Therapy ◽

Phase Iii ◽

Ecog Performance Status ◽

Double Blind

Abstract Background: Eastern Cooperative Oncology Group (ECOG) performance status is a prognostic factor in patients with multiple myeloma (MM). Lenalidomide (Len) is an oral immunomodulatory drug that is effective against relapsed/refractory MM (rrMM). In 2 prospective, randomized, double–blind, placebo–controlled phase III trials in patients with rrMM (MM–009 and MM–010), the combination of Len/Dexamethasone (Dex) induced a significantly higher overall response (OR) rate and complete response (CR) rate, as well as significantly longer overall survival (OS) and time–to–progression (TTP), compared with Dex alone. To investigate whether patients’ performance status has an impact on clinical response, we compared the efficacy and tolerability of Len/Dex in patients with baseline ECOG score =0 and >0. Methods: Data for patients with a baseline ECOG score recorded were pooled from the MM-009 and MM-010 studies (n= 690). Patients were randomized to receive Len (25 mg/day on days 1–21 of each 28–day cycle), or placebo. Both groups received Dex 40 mg PO q.d. on days 1–4, 9–12, and 17–20 (for the first 4 cycles). After 4 cycles, Dex 40 mg/day was administered only on days 1–4. Response to therapy, TTP, OS, and adverse events (AE) were assessed. Response rate and TTP are based on data obtained before unblinding (June 2005 [MM–009] and August 2005 [MM–010]). Results: Of 302 patients with an ECOG score of 0 at baseline, 152 were treated with Len/Dex and 150 with Dex alone. For those with an ECOG score >0, 192 received Len/Dex and 196 received Dex alone. Baseline characteristics were balanced between treatment groups. Patients with baseline ECOG score ≥0 had significantly higher OR rates with Len/Dex (59% and 62%, respectively) compared with Dex alone (both 22%; Table). In both ECOG groups, Len/Dex resulted in a significantly longer median TPP compared with Dex alone. In those with ECOG score >0, a significant improvement in OS was noted with Len/Dex treatment. No difference in median TTP was observed between patients with ECOG score ≥0 among Len/Dex-treated patients. Also, ECOG status did not affect tolerability profiles. Grade 3–4 hematological AE in patients with ECOG ≥0 treated with Len/Dex were higher than those treated with Dex alone and included neutropenia (31–39% vs 3–4%), thrombocytopenia (13–13% vs 4–8%), and anemia (9–12% vs 5–7%). Febrile neutropenia was reported in ≤3% of patients. Conclusion: Len/Dex was superior to Dex alone in patients with rrMM. This superiority of Len/Dex was irrespective of baseline performance status of the patients enrolled. Based on this analysis, we conclude that Len/Dex is an important therapeutic option in patients with rrMM despite suboptimal performance status. ECOG=0 ECOG>0 Len/Dex (n=152) Dex (n=150) P Len/Dex (n=192) Dex (n=196) P Clinical response, % OR 59 22 <0.001 62 22 <0.001 CR 12 1 <0.001 16 3 <0.001 PR 39 20 <0.001 35 18 <0.001 Median TTP, weeks 44.3 20.1 <0.001 57.0 20.1 <0.001 Median OS, weeks 156.0 159.1 NS 141.6 103.7 <0.01

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Phase I/II trial of dose-reduced capecitabine in elderly patients with advanced colorectal cancer

Current Oncology ◽

10.3747/co.24.3516 ◽

2017 ◽

Vol 24 (4) ◽

pp. 261 ◽

Cited By ~ 4

Author(s):

M.D. Vincent ◽

D. Breader ◽

M.C. Cripps ◽

D.J. Jonker ◽

P. Klimo ◽

...

Keyword(s):

Colorectal Cancer ◽

Phase I ◽

Advanced Colorectal Cancer ◽

Response Rate ◽

Performance Status ◽

Objective Response ◽

Eastern Cooperative Oncology Group ◽

Survival Duration ◽

Ecog Performance Status ◽

Pelvic Radiation

BackgroundCombination chemotherapy is associated with improved outcomes in trials of selected fit patients with advanced colorectal cancer (acrc). For older or less-fit patients, combination chemotherapy is associated with greater toxicity and less benefit. Capecitabine monotherapy is a reasonable option for those patients, but the optimal dose remains controversial.MethodsA multicentre phase i/ii trial of reduced-dose capecitabine (2000 mg/m2, days 1–14 every 21 days) was conducted in 221 patients representing one or more of the following subsets: age greater than 65 years (n = 167), Eastern Cooperative Oncology Group (ecog) performance status of 1 or greater (n = 139), elevated lactate dehydrogenase (ldh) (n = 105), or prior pelvic radiation (n = 54). Based on phase i results, patients with prior pelvic radiation received capecitabine 750 mg/m2 twice daily. The goal was to ascertain efficacy in a design that was unlikely to cause high levels of toxicity.Results Median age in the patient cohort was 72 years. A median of 5 and a mean of 8 capecitabine cycles were given (range: 0–50 cycles). Grade 3 or 4 toxicity occurred in 25% of patients during the first 3 cycles (8.1% hand–foot syndrome, 7.7% diarrhea). The response rate was 13.6%, with a 69.7% disease control rate. Median progression-free survival (pfs) was 5.6 months. Post progression, 56 patients received further capecitabine monotherapy (median of 4 additional cycles). Median overall survival duration for the patients was 14.3 months. Median survival was significantly higher for those who, at baseline, had an ecog performance status of 0 (compared with 1 or more) and normal ldh (compared with elevated ldh).Conclusions Toxicity is less with dose-reduced capecitabine than with historical full-dose capecitabine, with only a small trade-off in efficacy, seen as a lower objective response rate. The improved tolerability could lead to an increased number of cycles of therapy, and pfs appears to be consistently higher at the lower dose. Those observations should, in the absence of a head-to-head clinical trial, be viewed as compelling evidence that 1000 mg/m2, or even 750 mg/m2, twice daily is an appropriate dose in elderly or frail patients with acrc.

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Phase II Multicenter Study of Abiraterone Acetate Plus Prednisone Therapy in Patients With Docetaxel-Treated Castration-Resistant Prostate Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2009.25.9259 ◽

2010 ◽

Vol 28 (9) ◽

pp. 1496-1501 ◽

Cited By ~ 316

Author(s):

Daniel C. Danila ◽

Michael J. Morris ◽

Johann S. de Bono ◽

Charles J. Ryan ◽

Samuel R. Denmeade ◽

...

Keyword(s):

Performance Status ◽

Objective Response ◽

Eastern Cooperative Oncology Group ◽

Specific Antigen ◽

Circulating Tumor Cell ◽

Abiraterone Acetate ◽

Phase Iii ◽

Castration Resistant Prostate Cancer ◽

Ecog Performance Status ◽

Castration Resistant

Purpose Persistence of ligand-mediated androgen receptor signaling has been documented in castration-resistant prostate cancers (CRPCs). Abiraterone acetate (AA) is a potent and selective inhibitor of CYP17, which is required for androgen biosynthesis in the testes, adrenal glands, and prostate tissue. This trial evaluated the efficacy and safety of AA in combination with prednisone to reduce the symptoms of secondary hyperaldosteronism that can occur with AA monotherapy. Patients and Methods Fifty-eight men with progressive metastatic CRPC who experienced treatment failure with docetaxel-based chemotherapy received AA (1,000 mg daily) with prednisone (5 mg twice daily). Twenty-seven (47%) patients had received prior ketoconazole. The primary outcome was ≥ 50% prostate-specific antigen (PSA) decline, with objective response by Response Evaluation Criteria in Solid Tumors (RECIST) criteria, and changes in Eastern Cooperative Oncology Group (ECOG) performance status (PS) and circulating tumor cell (CTC) numbers. Safety was also evaluated. Results A ≥ 50% decline in PSA was confirmed in 22 (36%) patients, including 14 (45%) of 31 ketoconazole-naïve and seven (26%) of 27 ketoconazole-pretreated patients. Partial responses were seen in four (18%) of 22 patients with RECIST-evaluable target lesions. Improved ECOG PS was seen in 28% of patients. Median time to PSA progression was 169 days (95% CI, 82 to 200 days). CTC conversions with treatment from ≥ 5 to < 5 were noted in 10 (34%) of 29 patients. The majority of AA-related adverse events were grade 1 to 2, and no AA-related grade 4 events were seen. Conclusion AA plus prednisone was well tolerated, with encouraging antitumor activity in heavily pretreated CRPC patients. The incidence of mineralocorticoid-related toxicities (hypertension or hypokalemia) was reduced by adding low-dose prednisone. The combination of AA plus prednisone is recommended for phase III investigations.

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High-Dose Recombinant Interleukin 2 Therapy for Patients With Metastatic Melanoma: Analysis of 270 Patients Treated Between 1985 and 1993

Journal of Clinical Oncology ◽

10.1200/jco.1999.17.7.2105 ◽

1999 ◽

Vol 17 (7) ◽

pp. 2105-2105 ◽

Cited By ~ 1307

Author(s):

Michael B. Atkins ◽

Michael T. Lotze ◽

Janice P. Dutcher ◽

Richard I. Fisher ◽

Geoffrey Weiss ◽

...

Keyword(s):

Metastatic Melanoma ◽

Performance Status ◽

Objective Response ◽

Interleukin 2 ◽

Response Duration ◽

High Dose ◽

Large Tumor ◽

Median Response ◽

Recombinant Interleukin 2 ◽

Prior Systemic Therapy

PURPOSE: To determine the short- and long-term efficacy and toxicity of the high-dose intravenous bolus interleukin 2 (IL-2) regimen in patients with metastatic melanoma. PATIENTS AND METHODS: Two hundred seventy assessable patients were entered onto eight clinical trials conducted between 1985 and 1993. IL-2 (Proleukin [aldesleukin]; Chiron Corp, Emeryville, CA) 600,000 or 720,000 IU/kg was administered by 15-minute intravenous infusion every 8 hours for up to 14 consecutive doses over 5 days as clinically tolerated with maximum support, including pressors. A second identical treatment cycle was scheduled after 6 to 9 days of rest, and courses could be repeated every 6 to 12 weeks in stable or responding patients. Data were analyzed through fall 1996. RESULTS: The overall objective response rate was 16% (95% confidence interval, 12% to 21%); there were 17 complete responses (CRs) (6%) and 26 partial responses (PRs) (10%). Responses occurred with all sites of disease and in patients with large tumor burdens. The median response duration for patients who achieved a CR has not been reached and was 5.9 months for those who achieved a PR. Twelve (28%) of the responding patients, including 10 (59%) of the patients who achieved a CR, remain progression-free. Disease did not progress in any patient responding for more than 30 months. Baseline performance status and whether patients had received prior systemic therapy were the only predictive prognostic factors for response to IL-2 therapy. Toxicities, although severe, generally reversed rapidly after therapy was completed. Six patients (2%) died from adverse events, all related to sepsis. CONCLUSION: High-dose IL-2 treatment seems to benefit some patients with metastatic melanoma by producing durable CRs or PRs and should be considered for appropriately selected melanoma patients.

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Randomized phase II study of stereotactic body radiotherapy and interleukin-2 versus interleukin-2 in patients with metastatic melanoma

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-000773 ◽

2020 ◽

Vol 8 (1) ◽

pp. e000773 ◽

Cited By ~ 1

Author(s):

Brendan Curti ◽

Marka Crittenden ◽

Steven K Seung ◽

Christopher B Fountain ◽

Roxanne Payne ◽

...

Keyword(s):

Metastatic Melanoma ◽

Randomized Study ◽

Objective Response ◽

Interleukin 2 ◽

Evaluation Criteria ◽

Response Assessment ◽

Complete Response ◽

High Dose ◽

Randomized Phase Ii ◽

Registration Number

BackgroundA pilot study of stereotactic body radiation therapy (SBRT) followed by high-dose interleukin-2 (IL-2) showed a higher than anticipated objective response rate (ORR) among patients with metastatic melanoma (MM). We performed a prospective randomized study to determine if the ORR of SBRT + IL-2 was greater than IL-2 monotherapy in patients with advanced melanoma.MethodsPatients with MM who had adequate physiological reserve for IL-2 and at least one site suitable for SBRT were eligible. There was a 1:1 randomization to SBRT + IL-2 or IL-2 monotherapy. Patients received one or two doses of SBRT (20 Gy per fraction) with the last dose administered 3 days before starting the first cycle of IL-2. IL-2 (600,000 IU per kg via intravenous bolus infusion) was given every 8 hours for a maximum of 14 doses with a second cycle after a 2-week rest. Responding patients received up to six IL-2 cycles. Patients assigned to IL-2 monotherapy who exhibited progression of melanoma after cycle 2 were allowed to crossover and receive SBRT and additional IL-2. Response Evaluation Criteria in Solid Tumors 1.1 criteria were applied to non-irradiated lesions for response assessment.Results44 patients were included in the analysis. The ORR in the SBRT + IL-2 group was 54%: 21% complete response (CR), 33% partial response (PR), 21% stable disease (SD) and 25% progressive disease (PD). The ORR in patients receiving IL-2 monotherapy was 35%: 15% CR, 20% PR, 25% SD and 40% PD. Seven patients assigned to IL-2 subsequently received SBRT + IL-2. One CR and two PRs were observed in the crossover group. There was no difference in progression-free or overall survival (OS). At 5 years the OS was 26% in the SBRT + IL-2 group and 25% in the IL-2 monotherapy group. The disease control rate (DCR) was higher in the SBRT + IL-2 group (75% vs 60%, p=0.34).ConclusionsSBRT + IL-2 induced more objective responses with a higher DCR compared to IL-2 monotherapy in MM. IL-2 monotherapy resulted in a significantly higher ORR than anticipated. Some patients in the crossover group also achieved objective responses.Trial registration numberNCT01416831.

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Sequential chemoimmunotherapy with cisplatin, interleukin-2, and interferon alfa-2a for metastatic melanoma.

Journal of Clinical Oncology ◽

10.1200/jco.1993.11.11.2173 ◽

1993 ◽

Vol 11 (11) ◽

pp. 2173-2180 ◽

Cited By ~ 106

Author(s):

D Khayat ◽

C Borel ◽

J M Tourani ◽

A Benhammouda ◽

E Antoine ◽

...

Keyword(s):

Malignant Melanoma ◽

Performance Status ◽

Objective Response ◽

Eastern Cooperative Oncology Group ◽

Interleukin 2 ◽

Platinum Complex ◽

Metastatic Malignant Melanoma ◽

Interferon Alfa ◽

Ecog Performance Status ◽

Ifn Alpha

PURPOSE To evaluate the activity and the toxicity of the combination of cisplatin (CDDP)/recombinant interleukin-2 (rIL-2) and interferon alfa-2a (IFN alpha) in disseminated malignant melanoma (DMM). PATIENTS AND METHODS Between December 1990 and March 1992, 39 patients with biopsy-proven metastatic malignant melanoma (MM), bidimensionally measurable lesions and an Eastern Cooperative Oncology Group (ECOG) performance status < or = 2 entered this protocol. Seventy-nine percent had received previous chemotherapy including platinum complex (15%) and alpha interferon (44%). They received CDDP (100 mg/m2 on day 0) followed by IL-2 18.10(6) IU/m2/d continuous intravenous (IV) infusion from day 3 to day 6 and from day 17 to day 21. The cycle was repeated on day 28. Subcutaneous IFN alpha 9.10(6) IU three times weekly was administered throughout the treatment period. From day 66 or 94, patients were administered a maintenance cycle with CDDP 100 mg/m2, subcutaneous IL-2 5.10(6) IU/m2/d from day 15 to day 19 and from day 22 to day 26 and IFN alpha 9.10(6) IU three times weekly repeated every 5 weeks (maximum four cycles). RESULTS Among 39 assessable patients, five patients achieved complete responses (CRs). Sixteen patients had partial responses (PRs). The overall objective response rate was 53.8%. The number of metastatic sites was the only response-predictive factor. Toxicity was manageable in a routine patient setting and there was no life-threatening toxicity. CONCLUSION These results seem to indicate a possible synergy between CDDP/rIL-2 and IFN alpha in MM.

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TROG 18.01 phase III randomised clinical trial of the Novel Integration of New prostate radiation schedules with adJuvant Androgen deprivation: NINJA study protocol

BMJ Open ◽

10.1136/bmjopen-2019-030731 ◽

2019 ◽

Vol 9 (8) ◽

pp. e030731 ◽

Cited By ~ 3

Author(s):

Jarad Martin ◽

Paul Keall ◽

Shankar Siva ◽

Peter Greer ◽

David Christie ◽

...

Keyword(s):

Clinical Trial ◽

Controlled Trial ◽

Performance Status ◽

Androgen Deprivation ◽

Phase Iii ◽

High Dose ◽

The Novel ◽

Ecog Performance Status ◽

Initial Portion ◽

The Impact

IntroductionStereotactic body radiotherapy (SBRT) is a non-invasive alternative to surgery for the treatment of non-metastatic prostate cancer (PC). The objectives of the Novel Integration ofNew prostate radiation schedules with adJuvant Androgen deprivation (NINJA) clinical trial are to compare two emerging SBRT regimens for efficacy with technical substudies focussing on MRI only planning and the use of knowledge-based planning (KBP) to assess radiotherapy plan quality.Methods and analysisEligible patients must have biopsy-proven unfavourable intermediate or favourable high-risk PC, have an Eastern Collaborative Oncology Group (ECOG) performance status 0-1 and provide written informed consent. All patients will receive 6 months in total of androgen deprivation therapy. Patients will be randomised to one of two SBRT regimens. The first will be 40 Gy in five fractions given on alternating days (SBRT monotherapy). The second will be 20 Gy in two fractions given 1 week apart followed 2 weeks later by 36 Gy in 12 fractions given five times per week (virtual high-dose rate boost (HDRB)). The primary efficacy outcome will be biochemical clinical control at 5 years. Secondary endpoints for the initial portion of NINJA look at the transition of centres towards MRI only planning and the impact of KBP on real-time (RT) plan assessment. The first 150 men will demonstrate accrual feasibility as well as addressing the KBP and MRI planning aims, prior to proceeding with total accrual to 472 patients as a phase III randomised controlled trial.Ethics and disseminationNINJA is a multicentre cooperative clinical trial comparing two SBRT regimens for men with PC. It builds on promising results from several single-armed studies, and explores radiation dose escalation in the Virtual HDRB arm. The initial component includes novel technical elements, and will form an important platform set for a definitive phase III study.Trial registration numberANZCTN 12615000223538.

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Clinical evaluation of recombinant interferon alfa-2a (Roferon-A) in metastatic melanoma using two different schedules .

Journal of Clinical Oncology ◽

10.1200/jco.1987.5.8.1240 ◽

1987 ◽

Vol 5 (8) ◽

pp. 1240-1246 ◽

Cited By ~ 50

Author(s):

S S Legha ◽

N E Papadopoulos ◽

C Plager ◽

S Ring ◽

S P Chawla ◽

...

Keyword(s):

Performance Status ◽

Objective Response ◽

Eastern Cooperative Oncology Group ◽

Interferon Alfa ◽

Fixed Dose ◽

Ecog Performance Status ◽

Recombinant Interferon ◽

Level Of Activity ◽

Daily Schedule ◽

Major Toxicity

Based on the reports of activity of interferons against metastatic melanomas, we conducted a phase II study of recombinant interferon alfa-2a (Roferon-A, Hoffmann-La Roche, Nutley, NJ) in 66 patients with disseminated melanoma. All patients had excellent Eastern Cooperative Oncology Group (ECOG) performance status (0 to 1), and no evidence of brain metastases. Thirty patients had previously received chemotherapy and the remainder were untreated. The first 35 patients were treated on a daily schedule starting with a Roferon-A dose of 3 X 10(6) U/d and escalating to a maximum of 36 X 10(6) U/d over a period of 12 days. Because of excessive toxicity, the second group of 31 patients were treated on a fixed dose of 18 X 10(6) U/d [corrected] three times weekly (TIW). Among the 62 evaluable patients, five achieved an objective response for a response rate of 8% (95% confidence limits, 3% to 18%). Four patients had minor regressions and eight patients had stability of disease. The responses were evenly distributed between the two dose schedules. The major toxicity of interferon consisted of a constitutional syndrome of anorexia, fever, weight loss, and fatigue, which required a dose reduction in 75% of the patients on the daily schedule. Our data revealed a modest level of activity, which was not influenced by prior treatment or by the dose or schedule of interferon. Because of substantial toxicity with the daily schedule, we recommend a dose of 18 X 10(6) U/d [corrected] if interferon is used in the treatment of patients with melanoma.

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Results of treatment of 255 patients with metastatic renal cell carcinoma who received high-dose recombinant interleukin-2 therapy.

Journal of Clinical Oncology ◽

10.1200/jco.1995.13.3.688 ◽

1995 ◽

Vol 13 (3) ◽

pp. 688-696 ◽

Cited By ~ 878

Author(s):

G Fyfe ◽

R I Fisher ◽

S A Rosenberg ◽

M Sznol ◽

D R Parkinson ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Metastatic Renal Cell Carcinoma ◽

Renal Cell ◽

Objective Response ◽

Eastern Cooperative Oncology Group ◽

Interleukin 2 ◽

High Dose ◽

Primary Tumors ◽

Median Response

PURPOSE To determine the efficacy and toxicity of a high-dose interleukin-2 (IL-2) regimen in patients with metastatic renal cell carcinoma. PATIENTS AND METHODS Two hundred fifty-five assessable patients were entered onto seven phase II clinical trials. Proleukin (aldesleukin; Chiron Corp, Emeryville, CA) 600,000 or 720,000 IU/kg was administered by 15-minute intravenous (i.v.) infusion every 8 hours for up to 14 consecutive doses over 5 days as clinically tolerated with maximum support, including pressors. A second identical cycle of treatment was scheduled following 5 to 9 days of rest, and courses could be repeated every 6 to 12 weeks in stable or responding patients. RESULTS The overall objective response rate was 14% (90% confidence interval [CI], 10% to 19%), with 12 (5%) complete responses (CRs) and 24 (9%) partial responses (PRs). Responses occurred in all sites of disease, including bone, intact primary tumors, and visceral metastases, and in patients with large tumor burdens or bulky individual lesions. The median response duration for patients who achieved a CR has not been reached, but was 19.0 months for those who achieved a PR. Baseline Eastern Cooperative Oncology Group (ECOG) performance status (PS) was the only predictive prognostic factor for response to IL-2. While treatment was associated with severe acute toxicities, these generally reversed rapidly after therapy was completed. However, 4% of patients died of adverse events judged to be possibly or probably treatment-related. CONCLUSION High-dose IL-2 appears to benefit some patients with metastatic renal cell carcinoma by producing durable CRs or PRs. Despite severe acute treatment-associated toxicities, IL-2 should be considered for initial therapy of patients with appropriately selected metastatic renal cell carcinoma.

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