Salvage chemotherapy with mitomycin, docetaxel, and irinotecan (MDI regimen) in metastatic pancreatic adenocarcinoma

A phase I and II trial

Michele Reni, M. G. Panucci, P. Passoni, E. Bonetto, R. Nicoletti, M. Ronzoni, A. Zerbi, C. Staudacher, V. Di Carlo, E. Villa

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Background: This study evaluates the maximum tolerated dose (MTD) and activity of mitomycin, docetaxel, and irinotecan (MDI) regimen on metastatic pancreatic adenocarcinoma, previously treated with gemcitabine-containing chemotherapy. Patients and Methods: Patients with less than 76 years, Karnofsky performance status ≥60, and adequate bone marrow, kidney, and liver function were eligible for this trial. Treatment consisted of mitomycin 6 mg/m 2 day 1, docetaxel and irinotecan on days 2 and 8 with escalating doses, every 4 weeks. Dose levels were level 1:30 and 70 mg/m2; level 2:30 and 100 mg/m2; level 3:30 and 85 mg/m2; and level 4:35 and 85 mg/m2. Dose-limiting toxicity (DLT) was defined as grade 4 neutropenia >7 days, febrile neutropenia, grade 4 thrombocytopenia, nausea and vomiting, or diarrhea, grade ≥3 nonhematological toxicity, or failure to recover to grade ≤1 toxicity by day 43, occurring during the first cycle of chemotherapy. Results: Between September 2001 and October 2002, 15 eligible patients, three of whom had been previously treated with two lines of chemotherapy, received 33 cycles of MDI. Toxicity consisted of grade 3 to 4 neutropenia in 23% of cycles, fatigue, diarrhea, and vomiting in 10% of cycles, and one toxic death. DLT was observed in 2 of 6 level 2 patients (one toxic death and one grade 3 fatigue), and 2 of 3 level 4 patients (one neutropenic fever and one grade 3 fatigue). Thirteen patients were assessable for response. No objective response was observed among patients treated with MTD or higher doses. Three patients had stable disease; all other patients had progressive disease. The median time to tumor progression and median survival was 1.7 and 6.1 months, respectively. Conclusion: The MTD was mitomycin 6 mg/m2 day one, and docetaxel 30 and irinotecan 85 mg/m2 days 2 and 8. This regimen is inactive in metastatic pancreatic cancer.

Original languageEnglish
Pages (from-to)688-696
Number of pages9
JournalCancer Investigation
Volume22
Issue number5
DOIs
Publication statusPublished - 2004

Fingerprint

irinotecan
docetaxel
Mitomycin
Adenocarcinoma
Drug Therapy
Maximum Tolerated Dose
Fatigue
Poisons
gemcitabine
Neutropenia
Vomiting
Diarrhea
Karnofsky Performance Status
Febrile Neutropenia

Keywords

  • Docetaxel
  • Irinotecan
  • Metastatic disease
  • Mitomycin-C
  • Pancreatic cancer
  • Polichemotherapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Salvage chemotherapy with mitomycin, docetaxel, and irinotecan (MDI regimen) in metastatic pancreatic adenocarcinoma : A phase I and II trial. / Reni, Michele; Panucci, M. G.; Passoni, P.; Bonetto, E.; Nicoletti, R.; Ronzoni, M.; Zerbi, A.; Staudacher, C.; Di Carlo, V.; Villa, E.

In: Cancer Investigation, Vol. 22, No. 5, 2004, p. 688-696.

Research output: Contribution to journalArticle

Reni, M, Panucci, MG, Passoni, P, Bonetto, E, Nicoletti, R, Ronzoni, M, Zerbi, A, Staudacher, C, Di Carlo, V & Villa, E 2004, 'Salvage chemotherapy with mitomycin, docetaxel, and irinotecan (MDI regimen) in metastatic pancreatic adenocarcinoma: A phase I and II trial', Cancer Investigation, vol. 22, no. 5, pp. 688-696. https://doi.org/10.1081/CNV-200032929
Reni, Michele ; Panucci, M. G. ; Passoni, P. ; Bonetto, E. ; Nicoletti, R. ; Ronzoni, M. ; Zerbi, A. ; Staudacher, C. ; Di Carlo, V. ; Villa, E. / Salvage chemotherapy with mitomycin, docetaxel, and irinotecan (MDI regimen) in metastatic pancreatic adenocarcinoma : A phase I and II trial. In: Cancer Investigation. 2004 ; Vol. 22, No. 5. pp. 688-696.
@article{27f2ea32e23d4dcf8ad1615152a60430,
title = "Salvage chemotherapy with mitomycin, docetaxel, and irinotecan (MDI regimen) in metastatic pancreatic adenocarcinoma: A phase I and II trial",
abstract = "Background: This study evaluates the maximum tolerated dose (MTD) and activity of mitomycin, docetaxel, and irinotecan (MDI) regimen on metastatic pancreatic adenocarcinoma, previously treated with gemcitabine-containing chemotherapy. Patients and Methods: Patients with less than 76 years, Karnofsky performance status ≥60, and adequate bone marrow, kidney, and liver function were eligible for this trial. Treatment consisted of mitomycin 6 mg/m 2 day 1, docetaxel and irinotecan on days 2 and 8 with escalating doses, every 4 weeks. Dose levels were level 1:30 and 70 mg/m2; level 2:30 and 100 mg/m2; level 3:30 and 85 mg/m2; and level 4:35 and 85 mg/m2. Dose-limiting toxicity (DLT) was defined as grade 4 neutropenia >7 days, febrile neutropenia, grade 4 thrombocytopenia, nausea and vomiting, or diarrhea, grade ≥3 nonhematological toxicity, or failure to recover to grade ≤1 toxicity by day 43, occurring during the first cycle of chemotherapy. Results: Between September 2001 and October 2002, 15 eligible patients, three of whom had been previously treated with two lines of chemotherapy, received 33 cycles of MDI. Toxicity consisted of grade 3 to 4 neutropenia in 23{\%} of cycles, fatigue, diarrhea, and vomiting in 10{\%} of cycles, and one toxic death. DLT was observed in 2 of 6 level 2 patients (one toxic death and one grade 3 fatigue), and 2 of 3 level 4 patients (one neutropenic fever and one grade 3 fatigue). Thirteen patients were assessable for response. No objective response was observed among patients treated with MTD or higher doses. Three patients had stable disease; all other patients had progressive disease. The median time to tumor progression and median survival was 1.7 and 6.1 months, respectively. Conclusion: The MTD was mitomycin 6 mg/m2 day one, and docetaxel 30 and irinotecan 85 mg/m2 days 2 and 8. This regimen is inactive in metastatic pancreatic cancer.",
keywords = "Docetaxel, Irinotecan, Metastatic disease, Mitomycin-C, Pancreatic cancer, Polichemotherapy",
author = "Michele Reni and Panucci, {M. G.} and P. Passoni and E. Bonetto and R. Nicoletti and M. Ronzoni and A. Zerbi and C. Staudacher and {Di Carlo}, V. and E. Villa",
year = "2004",
doi = "10.1081/CNV-200032929",
language = "English",
volume = "22",
pages = "688--696",
journal = "Cancer Investigation",
issn = "0735-7907",
publisher = "Informa Healthcare",
number = "5",

}

TY - JOUR

T1 - Salvage chemotherapy with mitomycin, docetaxel, and irinotecan (MDI regimen) in metastatic pancreatic adenocarcinoma

T2 - A phase I and II trial

AU - Reni, Michele

AU - Panucci, M. G.

AU - Passoni, P.

AU - Bonetto, E.

AU - Nicoletti, R.

AU - Ronzoni, M.

AU - Zerbi, A.

AU - Staudacher, C.

AU - Di Carlo, V.

AU - Villa, E.

PY - 2004

Y1 - 2004

N2 - Background: This study evaluates the maximum tolerated dose (MTD) and activity of mitomycin, docetaxel, and irinotecan (MDI) regimen on metastatic pancreatic adenocarcinoma, previously treated with gemcitabine-containing chemotherapy. Patients and Methods: Patients with less than 76 years, Karnofsky performance status ≥60, and adequate bone marrow, kidney, and liver function were eligible for this trial. Treatment consisted of mitomycin 6 mg/m 2 day 1, docetaxel and irinotecan on days 2 and 8 with escalating doses, every 4 weeks. Dose levels were level 1:30 and 70 mg/m2; level 2:30 and 100 mg/m2; level 3:30 and 85 mg/m2; and level 4:35 and 85 mg/m2. Dose-limiting toxicity (DLT) was defined as grade 4 neutropenia >7 days, febrile neutropenia, grade 4 thrombocytopenia, nausea and vomiting, or diarrhea, grade ≥3 nonhematological toxicity, or failure to recover to grade ≤1 toxicity by day 43, occurring during the first cycle of chemotherapy. Results: Between September 2001 and October 2002, 15 eligible patients, three of whom had been previously treated with two lines of chemotherapy, received 33 cycles of MDI. Toxicity consisted of grade 3 to 4 neutropenia in 23% of cycles, fatigue, diarrhea, and vomiting in 10% of cycles, and one toxic death. DLT was observed in 2 of 6 level 2 patients (one toxic death and one grade 3 fatigue), and 2 of 3 level 4 patients (one neutropenic fever and one grade 3 fatigue). Thirteen patients were assessable for response. No objective response was observed among patients treated with MTD or higher doses. Three patients had stable disease; all other patients had progressive disease. The median time to tumor progression and median survival was 1.7 and 6.1 months, respectively. Conclusion: The MTD was mitomycin 6 mg/m2 day one, and docetaxel 30 and irinotecan 85 mg/m2 days 2 and 8. This regimen is inactive in metastatic pancreatic cancer.

AB - Background: This study evaluates the maximum tolerated dose (MTD) and activity of mitomycin, docetaxel, and irinotecan (MDI) regimen on metastatic pancreatic adenocarcinoma, previously treated with gemcitabine-containing chemotherapy. Patients and Methods: Patients with less than 76 years, Karnofsky performance status ≥60, and adequate bone marrow, kidney, and liver function were eligible for this trial. Treatment consisted of mitomycin 6 mg/m 2 day 1, docetaxel and irinotecan on days 2 and 8 with escalating doses, every 4 weeks. Dose levels were level 1:30 and 70 mg/m2; level 2:30 and 100 mg/m2; level 3:30 and 85 mg/m2; and level 4:35 and 85 mg/m2. Dose-limiting toxicity (DLT) was defined as grade 4 neutropenia >7 days, febrile neutropenia, grade 4 thrombocytopenia, nausea and vomiting, or diarrhea, grade ≥3 nonhematological toxicity, or failure to recover to grade ≤1 toxicity by day 43, occurring during the first cycle of chemotherapy. Results: Between September 2001 and October 2002, 15 eligible patients, three of whom had been previously treated with two lines of chemotherapy, received 33 cycles of MDI. Toxicity consisted of grade 3 to 4 neutropenia in 23% of cycles, fatigue, diarrhea, and vomiting in 10% of cycles, and one toxic death. DLT was observed in 2 of 6 level 2 patients (one toxic death and one grade 3 fatigue), and 2 of 3 level 4 patients (one neutropenic fever and one grade 3 fatigue). Thirteen patients were assessable for response. No objective response was observed among patients treated with MTD or higher doses. Three patients had stable disease; all other patients had progressive disease. The median time to tumor progression and median survival was 1.7 and 6.1 months, respectively. Conclusion: The MTD was mitomycin 6 mg/m2 day one, and docetaxel 30 and irinotecan 85 mg/m2 days 2 and 8. This regimen is inactive in metastatic pancreatic cancer.

KW - Docetaxel

KW - Irinotecan

KW - Metastatic disease

KW - Mitomycin-C

KW - Pancreatic cancer

KW - Polichemotherapy

UR - http://www.scopus.com/inward/record.url?scp=19944427916&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=19944427916&partnerID=8YFLogxK

U2 - 10.1081/CNV-200032929

DO - 10.1081/CNV-200032929

M3 - Article

VL - 22

SP - 688

EP - 696

JO - Cancer Investigation

JF - Cancer Investigation

SN - 0735-7907

IS - 5

ER -