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A phase I/II study of siltuximab (CNTO 328), an anti-interleukin-6 monoclonal antibody, in metastatic renal cell cancer.

Rossi JF, Négrier S, James ND, Kocak I, Hawkins R, Davis H, Prabhakar U, Qin X, Mulders P, Berns B - Br. J. Cancer (2010)

Bottom Line: Siltuximab was well tolerated overall, with no maximum tolerated dose or immune response observed.One PR was observed.Given the favourable safety profile of siltuximab and poor correlation of tumour shrinkage with clinical benefit demonstrated for other non-cytotoxic therapies, further evaluation of dose-escalation strategies and/or combination therapy may be considered for patients with RCC.

View Article: PubMed Central - PubMed

Affiliation: Service d'Hématologie et d'Oncologie Médicale, CHU Saint-Eloi, BT 509-INSERM U847, CHRU Montpellier et Université Montpelllier I, Montpellier, France.

ABSTRACT

Background: Serum interleukin (IL)-6 levels correlate with disease outcomes in renal cell carcinoma (RCC) patients. Siltuximab, a chimeric, murine-human mAb against IL-6, was evaluated in a three-part phase I/II study in patients with progressive metastatic RCC.

Methods: In part 1, 11 patients received 1, 3, 6, or 12mgkg-¹ at weeks 1, 4 and q2w × 2 thereafter; in part 2, 37 patients randomly received 3 or 6 mgkg-¹ q3w × 4; in part 3, 20 low-risk patients received 6mgkg-¹ q2w × 6. Modified WHO response criteria were assessed at weeks 7, 11, the 6-week follow-up, and when clinically indicated.

Results: Siltuximab was well tolerated overall, with no maximum tolerated dose or immune response observed. In all, 5 out of 11, 17 out of 37, and 9 out of 20 patients in parts 1, 2, and 3, respectively, received extended treatment beyond 4-6 initial infusions. In part 2, stable disease (SD) (≥11weeks) or better was achieved by 11 out of 17 (65%) 3 mgkg-¹ treated patients (one partial response (PR) ~8 months, 10 SD) and 10 out of 20 (50%) 6mgkg-¹ treated patients (10 SD). In part 3, documented complete or PR was not observed, but 13 out of 20 (65%) patients achieved SD.

Conclusion: Siltuximab stabilised disease in >50% of progressive metastatic RCC patients. One PR was observed. Given the favourable safety profile of siltuximab and poor correlation of tumour shrinkage with clinical benefit demonstrated for other non-cytotoxic therapies, further evaluation of dose-escalation strategies and/or combination therapy may be considered for patients with RCC.

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Maximal percentage of tumour reduction according to modified WHO criteria for patients in parts 2 and 3. Dotted lines at 25% and −25% represent the criteria for PD and PR, respectively. Two patients in the 3 mg kg–1 group in part 2 were not evaluable because neither had a week 11 radiologic assessment.
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fig3: Maximal percentage of tumour reduction according to modified WHO criteria for patients in parts 2 and 3. Dotted lines at 25% and −25% represent the criteria for PD and PR, respectively. Two patients in the 3 mg kg–1 group in part 2 were not evaluable because neither had a week 11 radiologic assessment.

Mentions: The maximum percentage of tumour reduction from baseline is shown for parts 2 and 3 combined in Figure 3. There was no significant difference in tumour reduction from baseline between patients treated with siltuximab administered at 3 mg kg–1 q2w, 6 mg kg–1 q2w, and 6 mg kg–1 q3w.


A phase I/II study of siltuximab (CNTO 328), an anti-interleukin-6 monoclonal antibody, in metastatic renal cell cancer.

Rossi JF, Négrier S, James ND, Kocak I, Hawkins R, Davis H, Prabhakar U, Qin X, Mulders P, Berns B - Br. J. Cancer (2010)

Maximal percentage of tumour reduction according to modified WHO criteria for patients in parts 2 and 3. Dotted lines at 25% and −25% represent the criteria for PD and PR, respectively. Two patients in the 3 mg kg–1 group in part 2 were not evaluable because neither had a week 11 radiologic assessment.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2967052&req=5

fig3: Maximal percentage of tumour reduction according to modified WHO criteria for patients in parts 2 and 3. Dotted lines at 25% and −25% represent the criteria for PD and PR, respectively. Two patients in the 3 mg kg–1 group in part 2 were not evaluable because neither had a week 11 radiologic assessment.
Mentions: The maximum percentage of tumour reduction from baseline is shown for parts 2 and 3 combined in Figure 3. There was no significant difference in tumour reduction from baseline between patients treated with siltuximab administered at 3 mg kg–1 q2w, 6 mg kg–1 q2w, and 6 mg kg–1 q3w.

Bottom Line: Siltuximab was well tolerated overall, with no maximum tolerated dose or immune response observed.One PR was observed.Given the favourable safety profile of siltuximab and poor correlation of tumour shrinkage with clinical benefit demonstrated for other non-cytotoxic therapies, further evaluation of dose-escalation strategies and/or combination therapy may be considered for patients with RCC.

View Article: PubMed Central - PubMed

Affiliation: Service d'Hématologie et d'Oncologie Médicale, CHU Saint-Eloi, BT 509-INSERM U847, CHRU Montpellier et Université Montpelllier I, Montpellier, France.

ABSTRACT

Background: Serum interleukin (IL)-6 levels correlate with disease outcomes in renal cell carcinoma (RCC) patients. Siltuximab, a chimeric, murine-human mAb against IL-6, was evaluated in a three-part phase I/II study in patients with progressive metastatic RCC.

Methods: In part 1, 11 patients received 1, 3, 6, or 12mgkg-¹ at weeks 1, 4 and q2w × 2 thereafter; in part 2, 37 patients randomly received 3 or 6 mgkg-¹ q3w × 4; in part 3, 20 low-risk patients received 6mgkg-¹ q2w × 6. Modified WHO response criteria were assessed at weeks 7, 11, the 6-week follow-up, and when clinically indicated.

Results: Siltuximab was well tolerated overall, with no maximum tolerated dose or immune response observed. In all, 5 out of 11, 17 out of 37, and 9 out of 20 patients in parts 1, 2, and 3, respectively, received extended treatment beyond 4-6 initial infusions. In part 2, stable disease (SD) (≥11weeks) or better was achieved by 11 out of 17 (65%) 3 mgkg-¹ treated patients (one partial response (PR) ~8 months, 10 SD) and 10 out of 20 (50%) 6mgkg-¹ treated patients (10 SD). In part 3, documented complete or PR was not observed, but 13 out of 20 (65%) patients achieved SD.

Conclusion: Siltuximab stabilised disease in >50% of progressive metastatic RCC patients. One PR was observed. Given the favourable safety profile of siltuximab and poor correlation of tumour shrinkage with clinical benefit demonstrated for other non-cytotoxic therapies, further evaluation of dose-escalation strategies and/or combination therapy may be considered for patients with RCC.

Show MeSH
Related in: MedlinePlus