Ifosfamide, cisplatin, and 13-Cis retinoic acid for patients with advanced or recurrent squamous cell carcinoma of the head and neck: A phase I-II study

Francesco Recchia, Angelo Lalli, Marco Lombardo, Sandro De Filippis, Gaetano Saggio, Francesca Fabbri, Michele Rosselli, Elisabetta Capomolla, Silvio Rea

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Abstract

BACKGROUND. Ifosfamide (IFO) and cisplatin (CDDP) are active drugs in the treatment of patients with squamous cell carcinoma (SCC) of the head and neck. 13-Cis retinoic acid (RA), along with its antiproliferative and differentiating activity on SCC cell lines, has immunomodulatory and chemopreventive effects. The objective of the current Phase I-II study was to evaluate the combination of CDDP, IFO, and RA in patients with advanced or recurrent SCC of the head and neck. METHODS. Patients with measurable recurrent, metastatic, or locally advanced SCC of the head and neck were eligible. Patients received a fixed dose of 20 mg/m2 CDDP, and IFO was administered with sodium mercaptoethanesolfonate in three-dose increments (1000 mg/m2, 1200 mg/m2, and 1500 mg/m2) up to dose limiting toxicity. Both drugs were given for 5 consecutive days every 3 weeks. RA (0.5 mg/kg) was given orally for 5 days per week. RESULTS. Fifty-two patients either with locoregional recurrence or distant metastases (50%) or with locally advanced SCC of the head and neck beyond surgery or radiation therapy (50%) were entered into the trial. Fifteen patients were enrolled in the Phase I study, during which the maximum tolerated dose of IFO was 1500 mg/m2. In the Phase II study (CDDP 20 mg/m2 and IFO 1200 mg/m2), the response rate was 72% (95% confidence interval, 57-83%). After a median follow-up of 23 months, the median time to disease progression was 10.4 months (range, 2.9-47.2+ months), and the median overall survival was 12.95 months (range, 1.7-47.2+ months). Two patients were converted from a partial response to a complete response with RA. Toxicity was relatively well tolerated and caused no deaths. Grade 3-4 neutropenia was observed in 16 patients, and Grade 2-3 diarrhea toxicity occurred in 9 patients. CONCLUSIONS. The dose and schedule for the combination of CDDP, IFO, and RA that were used in this study are feasible and active in the treatment of patients with SCC of the head and neck, with durable responses and a relatively well tolerated toxicity.

Original languageEnglish
Pages (from-to)814-821
Number of pages8
JournalCancer
Volume92
Issue number4
DOIs
Publication statusPublished - Aug 15 2001

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Isotretinoin
Ifosfamide
Cisplatin
Tretinoin
Carcinoma, squamous cell of head and neck
Maximum Tolerated Dose
Neutropenia
Pharmaceutical Preparations
Disease Progression
Squamous Cell Carcinoma
Diarrhea
Appointments and Schedules
Radiotherapy
Sodium
Confidence Intervals
Neoplasm Metastasis
Recurrence
Cell Line

Keywords

  • Chemotherapy
  • Cisplatin
  • Head and neck carcinoma
  • Ifosfamide
  • Retinoids

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Ifosfamide, cisplatin, and 13-Cis retinoic acid for patients with advanced or recurrent squamous cell carcinoma of the head and neck : A phase I-II study. / Recchia, Francesco; Lalli, Angelo; Lombardo, Marco; De Filippis, Sandro; Saggio, Gaetano; Fabbri, Francesca; Rosselli, Michele; Capomolla, Elisabetta; Rea, Silvio.

In: Cancer, Vol. 92, No. 4, 15.08.2001, p. 814-821.

Research output: Contribution to journalArticle

Recchia, Francesco ; Lalli, Angelo ; Lombardo, Marco ; De Filippis, Sandro ; Saggio, Gaetano ; Fabbri, Francesca ; Rosselli, Michele ; Capomolla, Elisabetta ; Rea, Silvio. / Ifosfamide, cisplatin, and 13-Cis retinoic acid for patients with advanced or recurrent squamous cell carcinoma of the head and neck : A phase I-II study. In: Cancer. 2001 ; Vol. 92, No. 4. pp. 814-821.
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abstract = "BACKGROUND. Ifosfamide (IFO) and cisplatin (CDDP) are active drugs in the treatment of patients with squamous cell carcinoma (SCC) of the head and neck. 13-Cis retinoic acid (RA), along with its antiproliferative and differentiating activity on SCC cell lines, has immunomodulatory and chemopreventive effects. The objective of the current Phase I-II study was to evaluate the combination of CDDP, IFO, and RA in patients with advanced or recurrent SCC of the head and neck. METHODS. Patients with measurable recurrent, metastatic, or locally advanced SCC of the head and neck were eligible. Patients received a fixed dose of 20 mg/m2 CDDP, and IFO was administered with sodium mercaptoethanesolfonate in three-dose increments (1000 mg/m2, 1200 mg/m2, and 1500 mg/m2) up to dose limiting toxicity. Both drugs were given for 5 consecutive days every 3 weeks. RA (0.5 mg/kg) was given orally for 5 days per week. RESULTS. Fifty-two patients either with locoregional recurrence or distant metastases (50{\%}) or with locally advanced SCC of the head and neck beyond surgery or radiation therapy (50{\%}) were entered into the trial. Fifteen patients were enrolled in the Phase I study, during which the maximum tolerated dose of IFO was 1500 mg/m2. In the Phase II study (CDDP 20 mg/m2 and IFO 1200 mg/m2), the response rate was 72{\%} (95{\%} confidence interval, 57-83{\%}). After a median follow-up of 23 months, the median time to disease progression was 10.4 months (range, 2.9-47.2+ months), and the median overall survival was 12.95 months (range, 1.7-47.2+ months). Two patients were converted from a partial response to a complete response with RA. Toxicity was relatively well tolerated and caused no deaths. Grade 3-4 neutropenia was observed in 16 patients, and Grade 2-3 diarrhea toxicity occurred in 9 patients. CONCLUSIONS. The dose and schedule for the combination of CDDP, IFO, and RA that were used in this study are feasible and active in the treatment of patients with SCC of the head and neck, with durable responses and a relatively well tolerated toxicity.",
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T1 - Ifosfamide, cisplatin, and 13-Cis retinoic acid for patients with advanced or recurrent squamous cell carcinoma of the head and neck

T2 - A phase I-II study

AU - Recchia, Francesco

AU - Lalli, Angelo

AU - Lombardo, Marco

AU - De Filippis, Sandro

AU - Saggio, Gaetano

AU - Fabbri, Francesca

AU - Rosselli, Michele

AU - Capomolla, Elisabetta

AU - Rea, Silvio

PY - 2001/8/15

Y1 - 2001/8/15

N2 - BACKGROUND. Ifosfamide (IFO) and cisplatin (CDDP) are active drugs in the treatment of patients with squamous cell carcinoma (SCC) of the head and neck. 13-Cis retinoic acid (RA), along with its antiproliferative and differentiating activity on SCC cell lines, has immunomodulatory and chemopreventive effects. The objective of the current Phase I-II study was to evaluate the combination of CDDP, IFO, and RA in patients with advanced or recurrent SCC of the head and neck. METHODS. Patients with measurable recurrent, metastatic, or locally advanced SCC of the head and neck were eligible. Patients received a fixed dose of 20 mg/m2 CDDP, and IFO was administered with sodium mercaptoethanesolfonate in three-dose increments (1000 mg/m2, 1200 mg/m2, and 1500 mg/m2) up to dose limiting toxicity. Both drugs were given for 5 consecutive days every 3 weeks. RA (0.5 mg/kg) was given orally for 5 days per week. RESULTS. Fifty-two patients either with locoregional recurrence or distant metastases (50%) or with locally advanced SCC of the head and neck beyond surgery or radiation therapy (50%) were entered into the trial. Fifteen patients were enrolled in the Phase I study, during which the maximum tolerated dose of IFO was 1500 mg/m2. In the Phase II study (CDDP 20 mg/m2 and IFO 1200 mg/m2), the response rate was 72% (95% confidence interval, 57-83%). After a median follow-up of 23 months, the median time to disease progression was 10.4 months (range, 2.9-47.2+ months), and the median overall survival was 12.95 months (range, 1.7-47.2+ months). Two patients were converted from a partial response to a complete response with RA. Toxicity was relatively well tolerated and caused no deaths. Grade 3-4 neutropenia was observed in 16 patients, and Grade 2-3 diarrhea toxicity occurred in 9 patients. CONCLUSIONS. The dose and schedule for the combination of CDDP, IFO, and RA that were used in this study are feasible and active in the treatment of patients with SCC of the head and neck, with durable responses and a relatively well tolerated toxicity.

AB - BACKGROUND. Ifosfamide (IFO) and cisplatin (CDDP) are active drugs in the treatment of patients with squamous cell carcinoma (SCC) of the head and neck. 13-Cis retinoic acid (RA), along with its antiproliferative and differentiating activity on SCC cell lines, has immunomodulatory and chemopreventive effects. The objective of the current Phase I-II study was to evaluate the combination of CDDP, IFO, and RA in patients with advanced or recurrent SCC of the head and neck. METHODS. Patients with measurable recurrent, metastatic, or locally advanced SCC of the head and neck were eligible. Patients received a fixed dose of 20 mg/m2 CDDP, and IFO was administered with sodium mercaptoethanesolfonate in three-dose increments (1000 mg/m2, 1200 mg/m2, and 1500 mg/m2) up to dose limiting toxicity. Both drugs were given for 5 consecutive days every 3 weeks. RA (0.5 mg/kg) was given orally for 5 days per week. RESULTS. Fifty-two patients either with locoregional recurrence or distant metastases (50%) or with locally advanced SCC of the head and neck beyond surgery or radiation therapy (50%) were entered into the trial. Fifteen patients were enrolled in the Phase I study, during which the maximum tolerated dose of IFO was 1500 mg/m2. In the Phase II study (CDDP 20 mg/m2 and IFO 1200 mg/m2), the response rate was 72% (95% confidence interval, 57-83%). After a median follow-up of 23 months, the median time to disease progression was 10.4 months (range, 2.9-47.2+ months), and the median overall survival was 12.95 months (range, 1.7-47.2+ months). Two patients were converted from a partial response to a complete response with RA. Toxicity was relatively well tolerated and caused no deaths. Grade 3-4 neutropenia was observed in 16 patients, and Grade 2-3 diarrhea toxicity occurred in 9 patients. CONCLUSIONS. The dose and schedule for the combination of CDDP, IFO, and RA that were used in this study are feasible and active in the treatment of patients with SCC of the head and neck, with durable responses and a relatively well tolerated toxicity.

KW - Chemotherapy

KW - Cisplatin

KW - Head and neck carcinoma

KW - Ifosfamide

KW - Retinoids

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