A phase I study of recombinant interferon gamma administered by s.c. injection three times per week in patients with solid tumours

Wagstaff, John; Smith, David B.; Nelmes, Philipp; Loynds, Peter; Crowther, Derek

doi:10.1007/bf00199301

Cited by 21 publications

(7 citation statements)

References 12 publications

(12 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast, many other tumors, among them SCLC, seem to resist cytokines, but they respond to IFNs in their early stage 28. One hypothesis is that the reset of the immune system in limited disease is faster than in extensive disease; this is also an explanation for the better response of limited disease in general.…”

Section: Discussionmentioning

confidence: 99%

Immunomodifiers in combination with conventional chemotherapy in small cell lung cancer: a Phase II, randomized study

Zarogoulidis¹,

Ziogas²,

Boutsikou³

et al. 2013

DDDT

View full text Add to dashboard Cite

PurposeTo evaluate the effect of immunotherapy on response, survival, and certain immune markers in patients with small cell lung cancer (SCLC) who are receiving chemotherapy.Patients and methodsPatients with SCLC (n = 164) were assigned to receive either chemotherapy alone (group A) or a combination of chemotherapy and immunotherapy as follows: interferon α (IFN-α; 3 million IU) 3 times per week (group B); IFN-γ (3 million IU) 3 times per week (group C); and IFN-α and IFN-γ (1.5 million IU of each) 3 times per week (group D). Chemotherapy was the same for all groups and consisted of eight cycles with carboplatin 5.5 mg/m2 intravenously on day 1, ifosfamide 3.5 mg/m2 intravenously on day 1, and etoposide 200 mg/m2 total dose taken orally on days 1 through 3, every 28 days. Patients completing chemotherapy were restaged, and those who were found to have limited disease received primary site and prophylactic cranial irradiation. Immunotherapy was continued throughout these treatments and during the follow-up period. Blood was taken before each course of chemotherapy and during follow-up to measure CD3+ lymphocytes, CD3+CD4+ lymphocytes, CD3+CD8+ lymphocytes, natural killer cells, and natural killer T cells.ResultsDifferences in response and survival were not significantly different when all patients were considered. However, among patients with limited disease, Kaplan–Meier analysis disclosed a survival benefit for group B (P , 0.05). The analysis of immunologic measurements revealed that the improvement of immune markers was always accompanied by clinical improvement, whereas deterioration of all markers was accompanied by disease progression (result not statistically significant except for group C; P , 0.05).ConclusionAmong cytokines used in the study, only IFN-α seems to confer a survival benefit to patients with SCLC with limited disease. However, immunotherapy remains a challenge in the treatment of lung neoplasms and should be further explored.

show abstract

Section: Discussionmentioning

confidence: 99%

Immunomodifiers in combination with conventional chemotherapy in small cell lung cancer: a Phase II, randomized study

Zarogoulidis¹,

Ziogas²,

Boutsikou³

et al. 2013

DDDT

View full text Add to dashboard Cite

show abstract

“…[16][17][18] Phase 1 and 2 studies of recombinant human interferon gamma-1b reported average overall response rates of 11.5 percent. [19][20][21][22][23] Interpreting these data is difficult because of differences in patient populations, treatment regimens, and the various interferon products used. Early studies of interferon gamma-1b used doses that approached or equaled the maximal tolerated doses.…”

Section: Discussionmentioning

confidence: 99%

“…Subsequent studies that used neopterin (a product of activated macrophages) and beta 2 -microglobulin (the light chain of the HLA-A complex) as surrogate markers of immune activation found a gaussian relation between the dose of interferon gamma-1b and its biologic effects, which suggested that doses below the maximal tolerated dose can produce optimal biologic effects. [23][24][25][26] A phase 1 study determined the optimal biologic dose of interferon gamma-1b (defined as the lowest dose inducing a maximal increase in neopterin and beta 2 -microglobulin) to be 100 m g subcutaneously once a week. 27 Using this low-dose regimen, Aulitzky et al 27 reported an overall response rate of 30 percent and a complete-response rate of 10 percent.…”

Section: Discussionmentioning

confidence: 99%

“…33 Phase 1 and 2 trials of interferon gamma-1b in metastatic renal-cell carcinoma reported overall response rates ranging from 0 to 33 percent (mean, 11.5 percent), results similar to those with interleukin-2 and interferon alfa. [19][20][21][22][23][24][25][26][27][28] A clinical trial to define an immunologically active regimen of interferon gamma-1b by means of biologic markers (neopterin and beta 2 -microglobulin) was reported in patients with malignant melanoma, and maximal increases in these markers were observed at a dose of 100 mg once per week. 8,34 A phase 1 study in patients with metastatic renal-cell carcinoma similarly found that the optimal biologic dose was 100 mg subcutaneously once per week and reported a 30 percent overall response and 10 percent completeresponse rate.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Interferon Gamma-1b Compared with Placebo in Metastatic Renal-Cell Carcinoma

et al. 1998

View full text Add to dashboard Cite

show abstract

“…Therefore, TMC-1 cells were moderately responsive to IFN-· and IFN-Á among the 7 tested gastric cancer cells included in this and our previous study. The effective concentrations of IFN-Á (0.5-50 units/ml) to suppress the growth of gastric cancer cells in vitro is clinically achievable [Gutterman et al, 1984;Wagstaff et al, 1987], whereas it is less likely to be achieved in patients who receive IFN-· [Jen et al, 2001]. Further studies by combining IFNs with other chemotherapeutic drugs may decrease the active doses of IFNs.…”

Section: Discussionmentioning

confidence: 99%

Establishment and Characterization of a Human Gastric Carcinoma Cell Line TMC-1

Shyu

Jiang

Jong

et al. 2004

Cells Tissues Organs

View full text Add to dashboard Cite

Established cancer cell lines are useful in the study of various cancers. We established a human gastric carcinoma cell line TMC-1 derived from the lymph node of a moderately differentiated adenocarcinoma of the stomach. TMC-1 cells grew in vitro as a mixture of attached and suspension cells, and exhibited spindle or ovoid morphology. They had a population doubling time of 15 h, a plating efficiency of 61%, formed colonies in semisolid agar, secreted the tumor marker CA 19-9, and were tumorigenic in athymic nude mice. The cells expressed E-cadherin and β-catenin. The karyotypic analysis demonstrated hyperdiploid features with a modal chromosome of 53. The cell had the deletion at chromosome 18q and gains at chromosome 2p13–25, 5p15, 5q21–35, 7, 8q24, 9q, 11, 12p, 14q24–32 and 20. Analysis by fluorescence in situ hybridization showed the deletion at 7qtel and duplication at 7q11.2 at the rearranged chromosome 7. Growth of TMC-1 cells was inhibited by 27–32% by interferon-α (2,000 U/ml) and by interferon-γ with an IC₅₀ of 125 U/ml. The cell line is tumorigenic in vivo, and its growth is moderately inhibited by interferon-α and interferon-γ. It can be used to develop new modalities of human gastric cancer treatment.

show abstract

A phase I study of recombinant interferon gamma administered by s.c. injection three times per week in patients with solid tumours

Cited by 21 publications

References 12 publications

Immunomodifiers in combination with conventional chemotherapy in small cell lung cancer: a Phase II, randomized study

Immunomodifiers in combination with conventional chemotherapy in small cell lung cancer: a Phase II, randomized study

Interferon Gamma-1b Compared with Placebo in Metastatic Renal-Cell Carcinoma

Establishment and Characterization of a Human Gastric Carcinoma Cell Line TMC-1

Contact Info

Product

Resources

About