Phase II trial of irinotecan plus cisplatin in patients with recurrent or metastatic squamous carcinoma of the head and neck

Abstract

BACKGROUND.Patients with recurrent or metastatic HNC have a poor response and survival with currently available chemotherapy agents. Thus, new agents are needed. The authors report the results of a phase II trial of irinotecan and cisplatin in patients with metastatic or recurrent HNC.METHODS.Patients were treated with irinotecan 65 mg/m2 IV over 90 minutes and cisplatin 30 mg/m2 were administered intravenously weekly for four weeks, followed by a two week rest. However, after 17 patients were treated with weekly irinotecan at a dose of 65 mg/m2, toxicity analysis demonstrated the poor tolerance of that dose in this patient population. Thus, the protocol was amended, and irinotecan was dose reduced to a starting dose of 50 mg/m2. Twenty‐three additional patients were treated with this dose.RESULTS.Forty patients were enrolled on study between February 2002 and April 2006, 17 patients at the first dose level and 23 patients at the amended dose level. Overall, 12 of 17 patients (71%) treated with irinotecan 65 mg/m2 experienced clinically significant grade 3 or 4 toxicity. Twelve patients required dose reductions. Toxicity was reduced but 17% of patients still experienced grade 3 or 4 toxicity on the lower irinotecan dose. The response rate was 35% for patients treated at irinotecan 65 mg/m2 and 22% for patients treated at 50 mg/m2. No complete responses were noted.CONCLUSIONS.The combination of irinotecan and cisplatin is efficacious in a poor prognosis group of patients but toxicity is substantial. Cancer 2008. © 2008 American Cancer Society.

Tumor relapse-free survival prognosis related consistency between cancer tissue and adjacent normal tissue in drug repurposing for solid tumor via connectivity map

“…In the context of HNSC, two drugs were identified using the PCS method (irinotecan, 69.71; paclitaxel, 83.71). In the case of irinotecan, two clinical trials (NCT00040807, NCT00639769) reported opposing treatment effects, aligning with the correct prediction [69, 70]. For paclitaxel, there were nine clinical trials (NCT00002632, NCT00003193, NCT00005087, NCT00011999, NCT00014118, NCT00095927, NCT00301028, NCT00392704, NCT01084083) supporting a treatment effect, while three clinical trials (NCT00002922, NCT00002888, NCT00006248) did not support a treatment effect, which represents an incorrect prediction by PCS[71–81].…”

Tumor relapse-free survival prognosis related consistency between cancer tissue and adjacent normal tissue in drug repurposing for solid tumor via connectivity map

“…In the context of HNSC, two drugs were identified using the PCS method (irinotecan, 69.71; paclitaxel, 83.71). In the case of irinotecan, two clinical trials (NCT00040807, NCT00639769) reported opposing treatment effects, aligning with the correct prediction [69, 70]. For paclitaxel, there were nine clinical trials (NCT00002632, NCT00003193, NCT00005087, NCT00011999, NCT00014118, NCT00095927, NCT00301028, NCT00392704, NCT01084083) supporting a treatment effect, while three clinical trials (NCT00002922, NCT00002888, NCT00006248) did not support a treatment effect, which represents an incorrect prediction by PCS[71–81].…”

An integrative somatic mutation analysis to identify pathways linked with survival outcomes across 19 cancer types

“…In addition, we found that some patients with overexpression of TOP1 in TCGA HNSC poor prognosis subgroup have developed therapy resistance against single chemotherapeutic agent such as Cisplatin. Interestingly, there is an ongoing trial in advanced HNSC showing efficacy of TOP1 inhibitor Irinotecan with Cisplatin in a poor prognosis patient subgroup 45 . These observations may suggest that TOP1 inhibitors-based combinations might offer an effective treatment option for HNSC patients with overexpression of TOP1 .…”

Cisplatin/Tegafur/Uracil/Irinotecan Triple Combination Therapy for Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma: A Phase I/II Clinical Study

“…Irinotecan, an analog of camptothecin that inhibits topoisomerase I, has high-potency antitumor activity [ 7 ]. In R/M HNSCC, the single use of irinotecan has demonstrated a modest overall response rate of 21.2%, and the combination of irinotecan and cisplatin is also effective [ 8 ]. To test the efficacy and safety of the cisplatin/UFUR/irinotecan triple combination regimen, we conducted a phase I/II trial to establish the dose-limiting toxicities, maximum tolerated dose (MTD), efficacy, and tolerability for patients with R/M HNSCC.…”

“…Other common adverse events, including diarrhea, nausea, and vomiting, were in line with expectations due to the known safety profile of these three drugs. In a previous study, Gilbert et al demonstrated some efficacy of the combination cisplatin and irinotecan, but toxicity restricted its routine use [ 8 ]. To compare with their regimen, we used a lower dose of irinotecan, but added one more agent, UFUR, a combination that proved to have a similar response with tolerable toxicity.…”

Tumor relapse-free survival prognosis related consistency between cancer tissue and adjacent normal tissue in drug repurposing for solid tumor via connectivity map

“…In the context of HNSC, two drugs were identified using the PCS method (irinotecan, 69.71; paclitaxel, 83.71). In the case of irinotecan, two clinical trials (NCT00040807, NCT00639769) reported opposing treatment effects, aligning with the correct prediction [69, 70]. For paclitaxel, there were nine clinical trials (NCT00002632, NCT00003193, NCT00005087, NCT00011999, NCT00014118, NCT00095927, NCT00301028, NCT00392704, NCT01084083) supporting a treatment effect, while three clinical trials (NCT00002922, NCT00002888, NCT00006248) did not support a treatment effect, which represents an incorrect prediction by PCS[71–81].…”

An integrative somatic mutation analysis to identify pathways linked with survival outcomes across 19 cancer types

“…In addition, we found that some patients with overexpression of TOP1 in TCGA HNSC poor prognosis subgroup have developed therapy resistance against single chemotherapeutic agent such as Cisplatin. Interestingly, there is an ongoing trial in advanced HNSC showing efficacy of TOP1 inhibitor Irinotecan with Cisplatin in a poor prognosis patient subgroup 45 . These observations may suggest that TOP1 inhibitors-based combinations might offer an effective treatment option for HNSC patients with overexpression of TOP1 .…”

Cisplatin/Tegafur/Uracil/Irinotecan Triple Combination Therapy for Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma: A Phase I/II Clinical Study

“…Irinotecan, an analog of camptothecin that inhibits topoisomerase I, has high-potency antitumor activity [ 7 ]. In R/M HNSCC, the single use of irinotecan has demonstrated a modest overall response rate of 21.2%, and the combination of irinotecan and cisplatin is also effective [ 8 ]. To test the efficacy and safety of the cisplatin/UFUR/irinotecan triple combination regimen, we conducted a phase I/II trial to establish the dose-limiting toxicities, maximum tolerated dose (MTD), efficacy, and tolerability for patients with R/M HNSCC.…”

“…Other common adverse events, including diarrhea, nausea, and vomiting, were in line with expectations due to the known safety profile of these three drugs. In a previous study, Gilbert et al demonstrated some efficacy of the combination cisplatin and irinotecan, but toxicity restricted its routine use [ 8 ]. To compare with their regimen, we used a lower dose of irinotecan, but added one more agent, UFUR, a combination that proved to have a similar response with tolerable toxicity.…”

Tumor relapse-free survival prognosis related consistency between cancer tissue and adjacent normal tissue in drug repurposing for solid tumor via connectivity map

“…In the context of HNSC, two drugs were identified using the PCS method (irinotecan, 69.71; paclitaxel, 83.71). In the case of irinotecan, two clinical trials (NCT00040807, NCT00639769) reported opposing treatment effects, aligning with the correct prediction [69, 70]. For paclitaxel, there were nine clinical trials (NCT00002632, NCT00003193, NCT00005087, NCT00011999, NCT00014118, NCT00095927, NCT00301028, NCT00392704, NCT01084083) supporting a treatment effect, while three clinical trials (NCT00002922, NCT00002888, NCT00006248) did not support a treatment effect, which represents an incorrect prediction by PCS[71–81].…”

An integrative somatic mutation analysis to identify pathways linked with survival outcomes across 19 cancer types

“…In addition, we found that some patients with overexpression of TOP1 in TCGA HNSC poor prognosis subgroup have developed therapy resistance against single chemotherapeutic agent such as Cisplatin. Interestingly, there is an ongoing trial in advanced HNSC showing efficacy of TOP1 inhibitor Irinotecan with Cisplatin in a poor prognosis patient subgroup 45 . These observations may suggest that TOP1 inhibitors-based combinations might offer an effective treatment option for HNSC patients with overexpression of TOP1 .…”

Cisplatin/Tegafur/Uracil/Irinotecan Triple Combination Therapy for Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma: A Phase I/II Clinical Study

“…Irinotecan, an analog of camptothecin that inhibits topoisomerase I, has high-potency antitumor activity [ 7 ]. In R/M HNSCC, the single use of irinotecan has demonstrated a modest overall response rate of 21.2%, and the combination of irinotecan and cisplatin is also effective [ 8 ]. To test the efficacy and safety of the cisplatin/UFUR/irinotecan triple combination regimen, we conducted a phase I/II trial to establish the dose-limiting toxicities, maximum tolerated dose (MTD), efficacy, and tolerability for patients with R/M HNSCC.…”

“…Other common adverse events, including diarrhea, nausea, and vomiting, were in line with expectations due to the known safety profile of these three drugs. In a previous study, Gilbert et al demonstrated some efficacy of the combination cisplatin and irinotecan, but toxicity restricted its routine use [ 8 ]. To compare with their regimen, we used a lower dose of irinotecan, but added one more agent, UFUR, a combination that proved to have a similar response with tolerable toxicity.…”