Survival, response and immune effects in a prospectively randomized study of dose strategy for alpha-N1 interferon

Silver, Hulbert K. B.; Connors, Joseph M.; Kong, So Jung; Karim, Kal; Jj, Spinelli

doi:10.1038/bjc.1988.309

Cited by 5 publications

(3 citation statements)

References 10 publications

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“…This study of the anti‐GD3 antibody R 24 examined the tumor biopsy compartments as well as the circulating lymphoid compartment and has revealed the potential importance of CD4 cells both in the endotumor compartment, as well as the peripheral blood. A correlation between the measured numbers of CD4 + cells and the CD4:CD8 cell distribution is similar to that which we have found to be prognostically important in patients receiving the IFNs 16, 20. The endotumor compartment of tumor biopsies demonstrated increased numbers of T cells among patients with objective clinical response and suggests that local T‐cell response is a determinant of antitumor response; neither peritumor nor perivascular T‐cell compartment showed this correlation.…”

Section: Discussionsupporting

confidence: 80%

Analysis of therapeutic and immunologic effects of R24 anti-GD3 monoclonal antibody in 37 patients with metastatic melanoma

Kirkwood

Mascari

Edington

et al. 2000

Cancer

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BACKGROUND Antitumor effects of antibodies against ganglioside antigens of melanoma have been reported, but neither optimal doses nor mechanisms have been established. METHODS This Phase IB trial of the murine immunoglobulin IgG3 monoclonal antibody R24 against disialoganglioside GD3 was conducted with 37 patients to define better the dose‐response relation and mechanism of action of R24 in patients with metastatic melanoma. RESULTS Dose‐limiting toxicity consisted of a pulmonary capillary leak syndrome in 3 of 5 patients in the 80 mg/M2/day dosage tier. Serial blood and tumor biopsy samples were obtained prior to therapy and on Days 5, 9, and 22 following R24 infusion. Tumor biopsy‐infiltrating lymphocytes were enumerated in peritumoral, endotumoral, and perivascular compartments: endotumoral CD4+ and CD8+ T cells and HLA‐DR+ T cells increased over time on R24 antibody. Endotumoral CD4 lymphoid infiltrate activation (DR expression) and antibody‐dependent cytotoxicity were the greatest in the one patient who achieved a complete response. CONCLUSIONS Clinical response was associated with depression in natural killer (CD56+ and CD56+DR+) blood cells (P = 0.03) and was associated with R24 dosage (P = 0.01). A complete response that lasted 2 years and a partial response that lasted 2 months occurred at a dose of 1 mg/M2/day. The limited number of clinical responses observed in this trial hampered the correlation of antitumor and immune parameters but provided a rational foundation for the future evaluation of antiganglioside antibodies. Cancer 2000;88:2693–702. © 2000 American Cancer Society.

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Section: Discussionsupporting

confidence: 80%

Analysis of therapeutic and immunologic effects of R24 anti-GD3 monoclonal antibody in 37 patients with metastatic melanoma

Kirkwood

Mascari

Edington

et al. 2000

Cancer

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“…The objective response rate in this study was one of the poorest, yet the median survival compared favorably with those of the previous studies. A fairly large propor tion of patients with disease stabilization might have con tributed to favorable survival as reported for other malig nancies [20]. It is possible that the survival would have further increased by prolongation of the interferon treat ment beyond the disease progression.…”

Section: Discussionmentioning

confidence: 99%

Disease Stabilization by Leukocyte Alpha Interferon and Survival of Patients with Metastatic Melanoma

Pyrhönen¹,

Kouri²,

Holsti³

et al. 1992

Oncology

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Thirty-one patients, 13 males and 18 females, with metastatic malignant melanoma were treated with human leukocyte interferon (IFN) alpha. The dose was 3 x 10⁶ IU daily s.c. for 6 weeks followed by 6 x 10⁶ IU/day 3 times a week. Only 1 patient (3%) achieved a partial response (PR) while 14 patients (45%) had disease stabilization for 2-8 months. Three patients experienced mixed responses, where some of the metastases responded, while the others were only stabilized. Interestingly, 1 patient showed regression of lung and disappearance of liver metastases after termination of IFN treatment. Two female patients are still alive without evidence of disease. After IFN they were treated with radiotherapy or surgery. The median survival for all the patients was 48 weeks. Our conclusion is that in IFN therapy long-term follow-up is indicated even in the absence of objective responses. In spite of poor response rate IFN may contribute beneficially to survival in a proportion of patients.

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“…The initial Phase IB trial accrued 27 patients with measurable metastatic melanoma, who entered 5 successively higher dosage tiers of 1,10,20,40, and 80 mg/M 2 /day in groups of 5-6 per dosage. Two objective antitumor responses observed in the lowest dosage tier of 1 mg/M 2 /day course led to the enrollment of a further 10 patients to treatment dosages geometrically bracketing the potentially active dosage of 1 mg/M 2 /day, i.e., 0.2 mg/M 2 /day, and 5 mg/M 2 /day.…”

Section: Patients and Therapy Schedulementioning

confidence: 99%

Analysis of therapeutic and immunologic effects of R24 anti‐GD3 monoclonal antibody in 37 patients with metastatic melanoma

Kirkwood

Mascari

Edington

et al. 2000

Cancer

View full text Add to dashboard Cite

Survival, response and immune effects in a prospectively randomized study of dose strategy for alpha-N1 interferon

Cited by 5 publications

References 10 publications

Analysis of therapeutic and immunologic effects of R24 anti-GD3 monoclonal antibody in 37 patients with metastatic melanoma

Analysis of therapeutic and immunologic effects of R24 anti-GD3 monoclonal antibody in 37 patients with metastatic melanoma

Disease Stabilization by Leukocyte Alpha Interferon and Survival of Patients with Metastatic Melanoma

Analysis of therapeutic and immunologic effects of R24 anti‐GD3 monoclonal antibody in 37 patients with metastatic melanoma

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