A phase II study of adriamycin in previously untreated squamous cell carcinoma of the head and neck

Cobleigh, Melody A.; Hill, James H.; Gallagher, Patricia A.; Kukla, Lawrence J.; Lad, Thomas E.; Shevrin, Daniel H.; Applebaum, Edward L.; McGuire, Wiliam P.

doi:10.1002/1097-0142(19851201)56:11<2573::aid-cncr2820561106>3.0.co;2-u

Cited by 11 publications

(6 citation statements)

References 5 publications

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“…5-FU is a thymidylate synthase inhibitor that inhibits cancer cell growth by the arresting cells in the S phase . Another anti-cancer drug, doxorubicin (DOX), is an anthracycline that exhibits its cytotoxic effects through the formation of covalent topoisomerase-DNA complexes, intercalating DNA, and/or inducing oxidative damage . A serious setback associated with use of DOX is the emergence of multi-drug resistance (MDR) phenotypes in cancer cells .…”

Section: Introductionmentioning

confidence: 99%

“…Another anti-cancer drug, doxorubicin (DOX), is an anthracycline that exhibits its cytotoxic effects through the formation of covalent topoisomerase-DNA complexes, intercalating DNA, and/or inducing oxidative damage . A serious setback associated with use of DOX is the emergence of multi-drug resistance (MDR) phenotypes in cancer cells . DOX, when administered individually, has demonstrated a response rate of 13-23% in phase II studies .…”

Section: Introductionmentioning

confidence: 99%

“…17 A serious setback associated with use of DOX is the emergence of multi-drug resistance (MDR) phenotypes in cancer cells. 17 DOX, when administered individually, has demonstrated a response rate of 13-23% in phase II studies. 17 The use of a high dose of DOX may overcome MDR, which in turn causes acute toxicities as well as dose-limiting cardiotoxicity.…”

Section: ■ Introductionmentioning

confidence: 99%

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Combinatorial Effects of Curcumin with an Anti-Neoplastic Agent on Head and Neck Squamous Cell Carcinoma Through the Regulation of EGFR-ERK1/2 and Apoptotic Signaling Pathways

2015

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Globally, head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer and represents approximately 6% of all diagnosed cancers. The use of anti-cancer drugs, such as docetaxel, doxorubicin (DOX), 5-fluorouracil (5-FU), and cisplatin (diammine dichloroplatinum(II), CDDP), is limited due to their non-specificity, drug resistance, and toxicity. A combinatorial approach may improve the efficacy of these chemotherapeutic drugs and reduce their non-specific toxicities. In the present study, curcumin, an anti-cancer phytochemical, was used in combination with 5-FU, doxorubicin, and cisplatin and their combinatorial effect on the HNSCC cell line NT8e was investigated. Our results showed that the combination of 5-FU or DOX with curcumin exhibited significant growth inhibition and enhanced apoptosis in NT8e cancer cells. Treatment with 5-FU or DOX in combination with curcumin induced apoptosis by inhibiting Bcl-2 and increasing Bax, caspase-3, and poly-ADP ribose polymerase (PARP) in NT8e cells. This was further confirmed through apoptotic characteristic features in cells, such as membrane blebbing, nuclear condensation, and cell shrinkage, as observed by DAPI staining and through decreased red/green fluorescence by JC-1. These two combinations also exhibited cell cycle growth arrest at the G1/S phase, which was confirmed by downregulation of cyclins (D1, E2, B1, and A2), CDK2, and increased p21 levels. In addition, curcumin exposure along with 5-FU or DOX inhibited cell proliferation through the downregulation of EGFR-ERK1/2 signaling molecules. Overall, our data demonstrates the promising therapeutic potential and underlying mechanisms of curcumin with 5-FU/DOX combinations as a new treatment modality for head and neck cancer management.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

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Combinatorial Effects of Curcumin with an Anti-Neoplastic Agent on Head and Neck Squamous Cell Carcinoma Through the Regulation of EGFR-ERK1/2 and Apoptotic Signaling Pathways

2015

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“…Both the toxicity profile and clinical benefit of this regimen could be better understood in a larger phase II/III trial. To this end, in this phase II trial, CR/PR rate of GEM/DOX treatment was 26%, which is higher than CR/PR rates of single GEM or DOX treatments with around 13% (4,5). Importantly, when compared to various other published combination studies in Phase II clinical trials for the treatment of recurrent or metastatic HNSCC (23-26), CR/PR rate obtained in response to GEM/DOX appears to be more efficacious.…”

Section: Discussionmentioning

confidence: 78%

“…Doxorubicin (DOX) is an anthracycline, which has 3 mechanisms of action: it induces the formation of covalent topoisomerase-DNA complexes, intercalates DNA, and/or causes oxidative damage. Single agent DOX has a demonstrated response rate of 13–23% in phase II studies (5). However, the efficacy of the GEM plus DOX combination (GEM/DOX) against HNSCC has not been previously studied.…”

Section: Introductionmentioning

confidence: 99%

Results of a Phase II Trial of Gemcitabine Plus Doxorubicin in Patients with Recurrent Head and Neck Cancers: Serum C18-Ceramide as a Novel Biomarker for Monitoring Response

Saddoughi

Garrett‐Mayer

Chaudhary

et al. 2011

Clinical Cancer Research

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Purpose Here we report a phase II clinical trial, which was designed to test a novel hypothesis that treatment with GEM/DOX would be efficacious via reconstitution of C18-ceramide signaling in HNSCC patients for whom first-line platinum-based therapy failed. Experimental Design Patients received GEM (1,000 mg/m2) and DOX (25 mg/m2) on days 1 and 8, every 21 days, until disease progression. After completion of 2 treatment cycles, patients were assessed radiographically, and serum samples were taken for sphingolipid measurements. Results We enrolled 18 patients in the trial, who were evaluable for toxicity, and 17 for response. The most common toxicity was neutropenia, observed in 9 of 18 patients, and there were no major non-hematological toxicities. Of the 17 patients, 5 patients had progressive disease (PD), 1 had complete response (CR), 3 exhibited partial response (PR), and 8 had stable disease (SD). The median progression-free survival (PFS) was 1.6 months (95% CI, 1.4, 4.2) with a median survival of 5.6 months (95% CI, 3.8, 18.2). Remarkably, serum sphingolipid analysis revealed significant differences in patterns of C18-ceramide elevation in patients with CR/PR/SD in comparison to patients with PD, indicating the reconstitution of tumor suppressor ceramide generation by GEM/DOX treatment. Conclusions Our data suggest that the GEM/DOX combination could represent an effective treatment for some patients with recurrent or metastatic HNSCC, and that serum C18-ceramide elevation might be a novel serum biomarker of chemotherapy response.

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Tumor Necrosis Factor and Cytotoxic Agents: Effect on Squamous Carcinoma Lines

Gapany

Dawson

Schriever³

et al. 1990

Archives of Otolaryngology - Head and Neck Surgery

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The cytotoxicity of dactinomycin (actinomycin D), doxorubicin hydrochloride (Adriamycin), cisplatin, fluorouracil, and methotrexate alone and in combination with recombinant human tumor necrosis factor (rHuTNF) on human squamous cell carcinoma lines was studied by an MTT proliferation assay. The rHuTNF alone caused no inhibition after 24 to 72 hours. All lines investigated showed a dose-dependent response to dactinomycin and doxorubicin. Potentiation of dactinomycin and doxorubicin cytotoxicity occurred with four of six cell lines following incubation of rHuTNF and the drug. No synergistic effect on cytotoxicity was seen with rHuTNF and any chemotherapeutic agent on two cell lines. The addition of rHuTNF did not augment the cytotoxic effect seen with cisplatin, methotrexate, or fluorouracil on any cell line. These results show that rHuTNF can enhance the cytotoxic effect of certain chemotherapeutic agents on squamous cell lines in vitro.

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A phase II study of adriamycin in previously untreated squamous cell carcinoma of the head and neck

Cited by 11 publications

References 5 publications

Combinatorial Effects of Curcumin with an Anti-Neoplastic Agent on Head and Neck Squamous Cell Carcinoma Through the Regulation of EGFR-ERK1/2 and Apoptotic Signaling Pathways

Combinatorial Effects of Curcumin with an Anti-Neoplastic Agent on Head and Neck Squamous Cell Carcinoma Through the Regulation of EGFR-ERK1/2 and Apoptotic Signaling Pathways

Results of a Phase II Trial of Gemcitabine Plus Doxorubicin in Patients with Recurrent Head and Neck Cancers: Serum C18-Ceramide as a Novel Biomarker for Monitoring Response

Tumor Necrosis Factor and Cytotoxic Agents: Effect on Squamous Carcinoma Lines

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