Combination Interleukin-2 and Doxorubicin in Advanced Adult Solid Tumors: Circumvention of Doxorubicin Resistance in Soft-Tissue Sarcoma?

Cesne, Axel Le; Vassal, Gilles; Farace, Françoise; Spielmann, M.; Chevalier, T. Le; Angevin, Eric; Valteau-Couanet, D; Fizazi, Karim; Cojean, I.; Llombard, A; Tursz, T; Escudier, Bernard

doi:10.1097/00002371-199905000-00010

Cited by 17 publications

(5 citation statements)

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“…IL-2 was also used to improve the anti-tumor activity of other forms of immunotherapy [143][144][145][146][147][148][149][150] chemotherapy [151][152][153][154][155][156] and surgery [157][158][159][160][161][162][163].…”

Section: Discussionmentioning

confidence: 99%

Gastric Cancer Immunotherapy: An Overview

Romano¹,

Uggeri²,

Nespoli³

et al. 2013

JCT

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Gastric adenocarcinoma is the third most common cancer and the second most common cause of death due to cancer worldwide. Surgery is still the major prognostic factor for gastric cancer. Patients who could not be resected have a poor prognosis with survival ranging from 3 to 11 months. There is evidence that surgical operations can cause a variety of immunological disturbances in man both in vivo and in vitro. The postoperative changes in the systemic immune response are proportional to the degree of surgical trauma leading to a generalized state of immunosuppression, which is implicated in the development of septic complications and provided a "fertile soil" for tumor cell metastasis. Immunotherapy may be a potentially promising alternative strategy for gastric cancer. In early clinical trials, systemic immunotherapy included both active vaccination directed against defined tumor-associated antigens expressed in gastric carcinoma cells and passive administration of IL-2 with some evidence of regression of metastatic gastric cancer. Other studies have applied immunotherapy in the adjuvant setting with equally promising results. For example, OK-432, a streptococcal preparation, demonstrated marginal improvement in survival for patients with stage III gastric cancer and a meta-analysis of centrally randomized controlled clinical trials indicated a significant survival benefit with combination OK-432 and chemotherapy compared to chemotherapy alone (p < 0.05). Additional data suggesting a biological and clinical benefit of subcutaneous, preoperative administration of low-dose IL-2 in colon cancer encouraged us to evaluate low-dose IL-2 therapy in the neoadjuvant setting for patients with gastric adenocarcinoma who undergo surgery and to evaluate its effects on systemic and tumor infiltrating lymphocyte numbers. We also sought to determine if neoadjuvant low-dose IL-2 could influence the clinical outcome for patients undergoing gastric resection for cancer. We report the biological, histological and clinical results with the full accrual of patients and a median follow-up of 51 months.

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Section: Discussionmentioning

confidence: 99%

Gastric Cancer Immunotherapy: An Overview

Romano¹,

Uggeri²,

Nespoli³

et al. 2013

JCT

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“…Of the 19 patients with metastatic tumors studied, 11 had non-small cell lung carcinomas, 5 had inflammatory breast cancer, 2 had osteosarcoma and 1 had colon adenocarcinoma. In another study, in 2 out of 21 patients with advanced solid tumors selective regimens with DOX plus IL2 induced objective responses [145]. It was found that CD4+ T helper cells and CD8+ T suppressor cells increased after the first week and decreased thereafter whereas CD16+ NK cells increased progressively during the 4 weeks of treatment.…”

Section: Studies In Humansmentioning

confidence: 94%

Anticancer Drug-Induced Immunomodulation and Cancer Therapeutics

Mihich

2007

CCTR

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In the light of increasing knowledge on the regulation of the efferent and afferent branches of antitumor immunity, on tumor-induced imbalances of immune response and on tumor escape mechanisms, it seem important to review the information available on the immunomodulating effects of anticancer drugs and their possible exploitation in cancer therapeutics.The immunomodulation induced by several antitumor antibiotics is considered with particular emphasis on the effects of Doxorubicin and their therapeutic exploitation. The immunomodulating effects of anticancer drugs considered include those of cyclophosphamide and other alkylating agents, of 6-mercaptopurine and other antimetabolities, of Vinca alkaloida, Taxanes, Thalidomide, Gleevec and Difluoromethyl ornithine. The positive effects on tumor immunity are discussed with reference to their potential exploitation in the therapeutics. The effects of certain anticancer drugs on tumor antigen expression are also discussed as a mechanism by which these agents increase tumor immunogenicity with consequent advantages for therapeutic exploitation and vaccine effectiveness. The need for increased molecular and clinical studies of anticancer drugs-induced immunomodulation is emphasized.

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“…Another study has applied DOX (40 mg/m 2 ) and PSC-833 (2 and 10 mg/kg) to suppress drug resistance and increase potential of DOX in cancer therapy [26]. In fact, studies recommend that DOX alone is not completely efficient in cancer eradication and polychemotherapy with other anti-tumor agents should be conducted to achieve best result [27][28][29]. Noteworthy, a clinical study has applied liposomal form of DOX with valspodar.…”

Section: Mechanisms Of Doxorubicin Resistance: An Overviewmentioning

confidence: 99%