Treatment with cisplatin and fluorouracil alternating with radiation favourably affects prognosis of inoperable squamous cell carcinoma of the head and neck: Results of a multivariate analysis on 273 patients

M. Benasso, L. Bonelli, G. Numico, R. Corvò, G. Sanguineti, R. Rosso, V. Vitale, M. Merlano

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Abstract

Purpose: The goal of the present analyses is to assess the association between different therapeutic approaches and both the probability of achieving a complete response and the risk of death in patients with state III-IV, inoperable, squamous cell carcinoma of the head and neck (SCC-HN). Patients and methods: Between August 1983 and December 1990, 273 patients with stage III-IV, previously untreated, unresectable SCC of the oral cavity, pharynx and larynx, were included into two consecutive randomized multi-institutional trials (HN-7 and HN-8 protocols) coordinated by the National Institute for Cancer Research (NICR) or Genoa. The HN-7 protocol compared neo-adjuvant chemotherapy (four cycles of vinblastine, 6 mg/m2 i.v. followed by bleomycin, 30 IU i.m. six hours later, day 1; methotrexate, 200 mg i.v., day 2; leucovorin, 45 mg orally, day 3) (VBM) followed by standard radiotherapy (70-75 Gy in 7-8 weeks) (55 patients) to alternating chemo-radiotherapy based on four cycles of the same chemotherapy alternated with three splits of radiation, 20 Gy each (61 patients). In the HN-8 protocol standard radiotherapy (77 patients) was compared to the same alternating program as the one used in the previous protocol but employing cisplatin, 20 mg/m2/day and fluorouracil, 200 mg/M2/day, bolus, both given for five consecutive days (CF) instead of VBM (80 patients). A single database was created with the patients on the two protocols. Age at diagnosis, gender site of the primary tumor, size of the primary, nodal involvement, performance status and treatment approach were analyzed by the multiple logistic regression model and the Cox regression method. The analyses were repeated including the treating institutions as a covariate (coordinated center versus others). Results: The multiple logistic regression analysis indicates that treatment (alternating more so than other, regardless of the chemotherapy regimen used) (P = 0.0001) is more likely to be associated with complete response. In addition, size of the primary tumor (P = 0.004), nodal involvement (P = 0.02) and performance status (P = 0.009) are prognostic variables affecting the probability of achieving a complete response. The Cox regression analysis indicates that treatment, performance status, size of the primary tumor, nodal involvement and, marginally, site of the primary tumor, are independent prognostic variables affecting the risk of death. When the radiation, alone therapy is adopted as the reference treatment, the relative risk of death is 0.58 (95% confidence interval (CI) 0.40-0.84) for alternating CF and radiation, 0.79 (95% CI 0.53-1.16) for alternating VBM and radiation and 1.30 (95% CI 0.89- 1.92) for sequential VBM and radiation. When the treating institution is included in the model, A 34% increased risk of death (P = 0.04) is observed for patients treated outside the coordinating center. Conclusion: In our series of patients and advanced, unresectable SCC-HN, treatment with cisplatin and fluorouracil alternating with radiation was associated with a more favourable prognosis. The role of the treating institution in the modulation of the treatment outcomes was also relevant.

Original languageEnglish
Pages (from-to)773-779
Number of pages7
JournalAnnals of Oncology
Volume8
Issue number8
DOIs
Publication statusPublished - Aug 1997

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Fluorouracil
Cisplatin
Multivariate Analysis
Radiation
Radiotherapy
Therapeutics
Logistic Models
Confidence Intervals
Neoplasms
Regression Analysis
Carcinoma, squamous cell of head and neck
Radiation Dosage
Drug Therapy
Leucovorin
National Cancer Institute (U.S.)
Vinblastine
Bleomycin
Adjuvant Chemotherapy
Larynx
Pharynx

Keywords

  • Chemo-radiotherapy
  • Head and neck cancer
  • Prognostic factors

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

@article{764f7a88d5704958ade74bb4cdac0f43,
title = "Treatment with cisplatin and fluorouracil alternating with radiation favourably affects prognosis of inoperable squamous cell carcinoma of the head and neck: Results of a multivariate analysis on 273 patients",
abstract = "Purpose: The goal of the present analyses is to assess the association between different therapeutic approaches and both the probability of achieving a complete response and the risk of death in patients with state III-IV, inoperable, squamous cell carcinoma of the head and neck (SCC-HN). Patients and methods: Between August 1983 and December 1990, 273 patients with stage III-IV, previously untreated, unresectable SCC of the oral cavity, pharynx and larynx, were included into two consecutive randomized multi-institutional trials (HN-7 and HN-8 protocols) coordinated by the National Institute for Cancer Research (NICR) or Genoa. The HN-7 protocol compared neo-adjuvant chemotherapy (four cycles of vinblastine, 6 mg/m2 i.v. followed by bleomycin, 30 IU i.m. six hours later, day 1; methotrexate, 200 mg i.v., day 2; leucovorin, 45 mg orally, day 3) (VBM) followed by standard radiotherapy (70-75 Gy in 7-8 weeks) (55 patients) to alternating chemo-radiotherapy based on four cycles of the same chemotherapy alternated with three splits of radiation, 20 Gy each (61 patients). In the HN-8 protocol standard radiotherapy (77 patients) was compared to the same alternating program as the one used in the previous protocol but employing cisplatin, 20 mg/m2/day and fluorouracil, 200 mg/M2/day, bolus, both given for five consecutive days (CF) instead of VBM (80 patients). A single database was created with the patients on the two protocols. Age at diagnosis, gender site of the primary tumor, size of the primary, nodal involvement, performance status and treatment approach were analyzed by the multiple logistic regression model and the Cox regression method. The analyses were repeated including the treating institutions as a covariate (coordinated center versus others). Results: The multiple logistic regression analysis indicates that treatment (alternating more so than other, regardless of the chemotherapy regimen used) (P = 0.0001) is more likely to be associated with complete response. In addition, size of the primary tumor (P = 0.004), nodal involvement (P = 0.02) and performance status (P = 0.009) are prognostic variables affecting the probability of achieving a complete response. The Cox regression analysis indicates that treatment, performance status, size of the primary tumor, nodal involvement and, marginally, site of the primary tumor, are independent prognostic variables affecting the risk of death. When the radiation, alone therapy is adopted as the reference treatment, the relative risk of death is 0.58 (95{\%} confidence interval (CI) 0.40-0.84) for alternating CF and radiation, 0.79 (95{\%} CI 0.53-1.16) for alternating VBM and radiation and 1.30 (95{\%} CI 0.89- 1.92) for sequential VBM and radiation. When the treating institution is included in the model, A 34{\%} increased risk of death (P = 0.04) is observed for patients treated outside the coordinating center. Conclusion: In our series of patients and advanced, unresectable SCC-HN, treatment with cisplatin and fluorouracil alternating with radiation was associated with a more favourable prognosis. The role of the treating institution in the modulation of the treatment outcomes was also relevant.",
keywords = "Chemo-radiotherapy, Head and neck cancer, Prognostic factors",
author = "M. Benasso and L. Bonelli and G. Numico and R. Corv{\`o} and G. Sanguineti and R. Rosso and V. Vitale and M. Merlano",
year = "1997",
month = "8",
doi = "10.1023/A:1008244110004",
language = "English",
volume = "8",
pages = "773--779",
journal = "Annals of Oncology",
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TY - JOUR

T1 - Treatment with cisplatin and fluorouracil alternating with radiation favourably affects prognosis of inoperable squamous cell carcinoma of the head and neck

T2 - Results of a multivariate analysis on 273 patients

AU - Benasso, M.

AU - Bonelli, L.

AU - Numico, G.

AU - Corvò, R.

AU - Sanguineti, G.

AU - Rosso, R.

AU - Vitale, V.

AU - Merlano, M.

PY - 1997/8

Y1 - 1997/8

N2 - Purpose: The goal of the present analyses is to assess the association between different therapeutic approaches and both the probability of achieving a complete response and the risk of death in patients with state III-IV, inoperable, squamous cell carcinoma of the head and neck (SCC-HN). Patients and methods: Between August 1983 and December 1990, 273 patients with stage III-IV, previously untreated, unresectable SCC of the oral cavity, pharynx and larynx, were included into two consecutive randomized multi-institutional trials (HN-7 and HN-8 protocols) coordinated by the National Institute for Cancer Research (NICR) or Genoa. The HN-7 protocol compared neo-adjuvant chemotherapy (four cycles of vinblastine, 6 mg/m2 i.v. followed by bleomycin, 30 IU i.m. six hours later, day 1; methotrexate, 200 mg i.v., day 2; leucovorin, 45 mg orally, day 3) (VBM) followed by standard radiotherapy (70-75 Gy in 7-8 weeks) (55 patients) to alternating chemo-radiotherapy based on four cycles of the same chemotherapy alternated with three splits of radiation, 20 Gy each (61 patients). In the HN-8 protocol standard radiotherapy (77 patients) was compared to the same alternating program as the one used in the previous protocol but employing cisplatin, 20 mg/m2/day and fluorouracil, 200 mg/M2/day, bolus, both given for five consecutive days (CF) instead of VBM (80 patients). A single database was created with the patients on the two protocols. Age at diagnosis, gender site of the primary tumor, size of the primary, nodal involvement, performance status and treatment approach were analyzed by the multiple logistic regression model and the Cox regression method. The analyses were repeated including the treating institutions as a covariate (coordinated center versus others). Results: The multiple logistic regression analysis indicates that treatment (alternating more so than other, regardless of the chemotherapy regimen used) (P = 0.0001) is more likely to be associated with complete response. In addition, size of the primary tumor (P = 0.004), nodal involvement (P = 0.02) and performance status (P = 0.009) are prognostic variables affecting the probability of achieving a complete response. The Cox regression analysis indicates that treatment, performance status, size of the primary tumor, nodal involvement and, marginally, site of the primary tumor, are independent prognostic variables affecting the risk of death. When the radiation, alone therapy is adopted as the reference treatment, the relative risk of death is 0.58 (95% confidence interval (CI) 0.40-0.84) for alternating CF and radiation, 0.79 (95% CI 0.53-1.16) for alternating VBM and radiation and 1.30 (95% CI 0.89- 1.92) for sequential VBM and radiation. When the treating institution is included in the model, A 34% increased risk of death (P = 0.04) is observed for patients treated outside the coordinating center. Conclusion: In our series of patients and advanced, unresectable SCC-HN, treatment with cisplatin and fluorouracil alternating with radiation was associated with a more favourable prognosis. The role of the treating institution in the modulation of the treatment outcomes was also relevant.

AB - Purpose: The goal of the present analyses is to assess the association between different therapeutic approaches and both the probability of achieving a complete response and the risk of death in patients with state III-IV, inoperable, squamous cell carcinoma of the head and neck (SCC-HN). Patients and methods: Between August 1983 and December 1990, 273 patients with stage III-IV, previously untreated, unresectable SCC of the oral cavity, pharynx and larynx, were included into two consecutive randomized multi-institutional trials (HN-7 and HN-8 protocols) coordinated by the National Institute for Cancer Research (NICR) or Genoa. The HN-7 protocol compared neo-adjuvant chemotherapy (four cycles of vinblastine, 6 mg/m2 i.v. followed by bleomycin, 30 IU i.m. six hours later, day 1; methotrexate, 200 mg i.v., day 2; leucovorin, 45 mg orally, day 3) (VBM) followed by standard radiotherapy (70-75 Gy in 7-8 weeks) (55 patients) to alternating chemo-radiotherapy based on four cycles of the same chemotherapy alternated with three splits of radiation, 20 Gy each (61 patients). In the HN-8 protocol standard radiotherapy (77 patients) was compared to the same alternating program as the one used in the previous protocol but employing cisplatin, 20 mg/m2/day and fluorouracil, 200 mg/M2/day, bolus, both given for five consecutive days (CF) instead of VBM (80 patients). A single database was created with the patients on the two protocols. Age at diagnosis, gender site of the primary tumor, size of the primary, nodal involvement, performance status and treatment approach were analyzed by the multiple logistic regression model and the Cox regression method. The analyses were repeated including the treating institutions as a covariate (coordinated center versus others). Results: The multiple logistic regression analysis indicates that treatment (alternating more so than other, regardless of the chemotherapy regimen used) (P = 0.0001) is more likely to be associated with complete response. In addition, size of the primary tumor (P = 0.004), nodal involvement (P = 0.02) and performance status (P = 0.009) are prognostic variables affecting the probability of achieving a complete response. The Cox regression analysis indicates that treatment, performance status, size of the primary tumor, nodal involvement and, marginally, site of the primary tumor, are independent prognostic variables affecting the risk of death. When the radiation, alone therapy is adopted as the reference treatment, the relative risk of death is 0.58 (95% confidence interval (CI) 0.40-0.84) for alternating CF and radiation, 0.79 (95% CI 0.53-1.16) for alternating VBM and radiation and 1.30 (95% CI 0.89- 1.92) for sequential VBM and radiation. When the treating institution is included in the model, A 34% increased risk of death (P = 0.04) is observed for patients treated outside the coordinating center. Conclusion: In our series of patients and advanced, unresectable SCC-HN, treatment with cisplatin and fluorouracil alternating with radiation was associated with a more favourable prognosis. The role of the treating institution in the modulation of the treatment outcomes was also relevant.

KW - Chemo-radiotherapy

KW - Head and neck cancer

KW - Prognostic factors

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