Chemotherapy in Locally Advanced, Squamous Cell Head and Neck Cancer: Limitations, Lessons Learned, and Evolving Standards of Care

6073 Background: Cisplatin/infusional 5-fluorouracil chemotherapy is routinely administered as standard induction chemotherapy in advanced HANC. However, the optimum treatment remains to be defined. Gemcitabine is an active agent in HANC and few studies have evaluated induction GC in HANC. We have explored the activity and toxicity of GC as induction treatment in HANC and report the results. Methods: From August 2005 to September 2006, 55 patients with locally advanced HANC had induction chemotherapy with GC at Shaukat Khanum Memorial Cancer Hospital and Research Centre. We reviewed the medical records and prospectively collected data to determine activity and toxicity of induction GC. M:F ratio was 64%:36% with a median age of 50 years (range 19–80). All patients had histologically confirmed squamous cell carcinoma. The site of disease was nasopharynx, paranasal sinuses, oral cavity, oropharynx, larynx and hyopharynx in 4% (2), 11% (6), 51% (21), 2% (1), 11% (6) and 22% (11) respectively. According to AJCC staging 7% (4) had stage III and 93% (51) had stage IVa/IVb disease (T3N0 7%, T3N+ 2%, T4N0 38% and T4N+ 53%). Induction chemotherapy consisted of 2 cycles of cisplatin 75 mg/m2 day 1 and gemcitabine 1000 mg/m2 day 1 and 8 with treatment repeated three weekly. Fifty-three (94%) patients received 2 cycles as planned. Toxicity was scored after each cycle according to the NCI.CTC criteria. Response was assessed following completion of induction chemotherapy by clinical examination/MRI scan. Results: All patients were available for assessment of toxicity and response. A total of 111 cycles were delivered. The response rates are: complete 24% (13), partial 62% (34), no response 7% (4) and progression 7% (4). The overall response rate was 86% (complete 24%, partial 62%). No treatment related deaths occurred. Haematological G3/G4 toxicity included neutropenia (13%/7%) and thrombocytopenia (5%/0%). The non-haematological toxicity observed (nausea, vomiting and diarrhoea) was only G1/G2. Conclusions: GC is well tolerated with low toxicity and high anti tumour activity as neoadjuvant chemotherapy treatment in squamous cell head and neck cancer. Combination GC arm should be included in future trials. No significant financial relationships to disclose.

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Clinical benefits of concurrent capecitabine and cisplatin versus concurrent cisplatin and 5-flurouracil in locally advanced squamous cell head and neck cancer

Drug Discoveries & Therapeutics ◽

10.5582/ddt.2013.v7.1.36 ◽

2013 ◽

Vol 7 (1) ◽

Cited By ~ 12

Author(s):

Seema Gupta

Keyword(s):

Head And Neck Cancer ◽

Head And Neck ◽

Neck Cancer ◽

Squamous Cell ◽

Locally Advanced ◽

Clinical Benefits

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Faculty Opinions recommendation of Randomized phase II study of cisplatin and 5-FU continuous infusion (PF) versus cisplatin, UFT and vinorelbine (UFTVP) as induction chemotherapy in locally advanced squamous cell head and neck cancer (LA-SCHNC).

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1091255.545674 ◽

2007 ◽

Author(s):

Athanassios Argiris

Keyword(s):

Head And Neck Cancer ◽

Head And Neck ◽

Continuous Infusion ◽

Induction Chemotherapy ◽

Phase Ii ◽

Neck Cancer ◽

Squamous Cell ◽

Phase Ii Study ◽

Locally Advanced ◽

Randomized Phase Ii

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Association between standardized uptake value and survival in patients with locally advanced or metastatic squamous cell head and neck cancer

Journal of Oncological Sciences ◽

10.1016/j.jons.2015.11.003 ◽

2016 ◽

Vol 1 ◽

pp. 1-4

Author(s):

Zeynep Oruc ◽

M. Emin Buyukbayram ◽

Muhammet Ali Kaplan ◽

Zuhat Urakcı ◽

Mehmet Küçüköner ◽

...

Keyword(s):

Head And Neck Cancer ◽

Head And Neck ◽

Neck Cancer ◽

Squamous Cell ◽

Locally Advanced ◽

Standardized Uptake Value

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Modulation of the antitumor effect of methotrexate by low-dose leucovorin in squamous cell head and neck cancer: a randomized placebo-controlled clinical trial.

Journal of Clinical Oncology ◽

10.1200/jco.1990.8.2.203 ◽

1990 ◽

Vol 8 (2) ◽

pp. 203-208 ◽

Cited By ~ 34

Author(s):

G P Browman ◽

M D Goodyear ◽

M N Levine ◽

R Russell ◽

S D Archibald ◽

...

Keyword(s):

Head And Neck Cancer ◽

Head And Neck ◽

Neck Cancer ◽

Squamous Cell ◽

Antitumor Effect ◽

Locally Advanced ◽

Eastern Cooperative Oncology Group ◽

Controlled Clinical Trial ◽

High Dose ◽

Dose Methotrexate

Randomized trials comparing high-dose methotrexate (HDMTX) plus leucovorin (LV) with standard-dose methotrexate (SDMTX) have not detected a therapeutic advantage for the HDMTX arm despite compelling evidence from experimental systems. We hypothesized that these negative trials might reflect modulation of the antitumor effect of methotrexate (MTX) by LV. To test this we randomized 61 patients with locally advanced and recurrent squamous cell head and neck cancer to receive SDMTX (40 mg/m2 weekly for 8 weeks) and either LV or placebo "rescue" starting 24 hours later. Of the 61 randomized patients, there were protocol violations in two cases, leaving 59 patients evaluable for response using standard criteria, and for toxicity using the Eastern Cooperative Oncology Group (ECOG) scale. Of the 29 patients randomized to MTX plus LV, there were five responders (17.2%) compared with 11 of 30 (36.7%) patients randomized to MTX plus placebo (P = .047). Response was influenced independently by age, gender, and by previous treatment. Toxicity overall was more severe in patients randomized to MTX plus placebo (P = .016). This was accounted for primarily by differences in toxicities related to bone marrow function (neutrophil and platelet counts), stomatitis, and elevations of liver function tests. MTX therapy was more often interrupted for toxicity in the placebo group (P = .007) and discontinued for progressive disease in the LV group (P = .07). These results indicate that at the doses of MTX and LV used, LV modulates the antitumor effect as well as the toxicity of MTX in patients with head and neck cancer.

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Phase I Trial of Gefitinib in Combination With Radiation or Chemoradiation for Patients With Locally Advanced Squamous Cell Head and Neck Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2007.12.9650 ◽

2007 ◽

Vol 25 (31) ◽

pp. 4880-4886 ◽

Cited By ~ 46

Author(s):

Changhu Chen ◽

Madeleine Kane ◽

John Song ◽

John Campana ◽

Adam Raben ◽

...

Keyword(s):

Head And Neck Cancer ◽

Head And Neck ◽

Neck Cancer ◽

Squamous Cell ◽

Concurrent Chemoradiotherapy ◽

Locally Advanced ◽

Intermediate Stage ◽

Concomitant Boost ◽

Grade 3 ◽

Boost Radiation

PurposeTo establish the safety and toxicity profile of daily gefitinib with radiation alone or with concurrent chemoradiotherapy in previously untreated patients with locally advanced squamous cell head and neck cancer (LAHNC).Patients and MethodsPatients with intermediate-stage LAHNC were treated with concomitant boost radiation (RT) alone with escalating doses of daily gefitinib (250 or 500 mg; cohort I). Once a safety profile was determined with RT alone, patients with high-risk disease were then treated with daily gefitinib (250 or 500 mg), weekly cisplatin (CDDP; 30 mg/m2), and once-daily RT (cohort II). Patients also received post-RT gefitinib at 250 mg daily for a period of up to 2 years.ResultsTwenty-three patients were enrolled and assessable for toxicity. No dose-limiting toxicities (DLTs) were observed in patients treated in cohort I at either 250 or 500 mg of gefitinib daily with concomitant boost RT to 72 Gy. In patients receiving chemoradiotherapy and gefitinib (cohort II), DLTs included one grade 4 diarrhea and one grade 4 neutropenic fever. Fifteen patients started maintenance gefitinib, and eight (53%) experienced grade 1 to 2 acne-like skin rash and diarrhea, but no grade 3 or 4 toxicity occurred.ConclusionGefitinib (250 or 500 mg daily) was well tolerated with concomitant boost RT or concurrent chemoradiotherapy with weekly CDDP. Protracted administration of gefitinib for up to 2 years at 250 mg daily was also tolerated well.

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