levoleucovorin and Laryngeal-Neoplasms

This paper presents an overview of studies of therapy of head and neck squamous cell carcinoma in which chemotherapy was combined with other modalities. The rationale for using chemotherapy with surgery is discussed, but ststematic studies of this combination of modalities have not been reported. Systemic chemotherapy plus radiation therapy has been studied using hydrozyurea, t-fluorouracil (5-FU), and methotrexate (MTX). Uncontrolled studies with hydroxyurea report favorable results, but a well-controlled study gave negative results. Controlled studies with 5-FU have given favorable results in certain tumor stages and sites of origin. MTX plus radiation in a small series produced slightly better survival than radiation alone. Intra-arterial chemotherapy plus radiation therapy has been the subject of exploratory studies but no firm conclusions can be drawn from these studies. Chemotherapy plus immunotherapy has been explored and merits further study. Based on the studies reported to date one can suggest the need for large-scale randomized control studies of long-term chemotherapy combined with other modalities.

Topics: Bleomycin; Carcinoma, Squamous Cell; Cyclophosphamide; Fluorouracil; Head; Head and Neck Neoplasms; Humans; Hydroxyurea; Immunotherapy; Laryngeal Neoplasms; Leucovorin; Methotrexate; Neoplasm Metastasis; Neoplasms; Radiotherapy; Vinblastine

Topics: Bleomycin; Carcinoma, Squamous Cell; Drug Administration Schedule; Drug Therapy, Combination; Fluorouracil; Head and Neck Neoplasms; Humans; Hydroxyurea; Laryngeal Neoplasms; Leucovorin; Lip Neoplasms; Lymphatic Metastasis; Methotrexate; Mouth Neoplasms; Nasopharyngeal Neoplasms; Tongue Neoplasms

This is a retrospective study of laryngeal preservation in endolaryngeal cancer with induction chemotherapy and radiotherapy for good responders. Between 1985 and 1995, 104 patients were treated in Institut Gustave Roussy (87 patients) and in Limoges (17 patients). The overall survival for the whole population was 76% and 69% at 3 and 5 years respectively, with a 36% rate of laryngeal preservation. In this retrospective series of patients, the single prognostic factor affecting survival was arytenoid mobility before treatment (66% and 55% at 3 years vs 85% and 82% at 5 years; p<0.004). Loco-regional failures were higher (33% vs 15%, p<0.03), and laryngeal preservation was lower (18% vs 51%) among patients with a fixed arytenoid (49 pts), compared with patients with a non fixed arytenoid (55 pts) ). The percentages of patients with a fixed arytenoid could explain the conflicting results of the two randomized studies of laryngeal preservation in laryngeal cancer.

Topics: Antibiotics, Antineoplastic; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Arytenoid Cartilage; Bleomycin; Cisplatin; Combined Modality Therapy; Data Interpretation, Statistical; Fluorouracil; Humans; Laryngeal Neoplasms; Laryngectomy; Leucovorin; Lymphatic Metastasis; Neoplasm Metastasis; Prognosis; Radiotherapy Dosage; Retrospective Studies; Survival Analysis; Time Factors

To analyze clinical and pharmacokinetic data of cisplatin (CP)/fluorouracil (FU)/l folinic acid (l FA) chemotherapy administered as first-line treatment to locally advanced head and neck cancer patients.. Thirty-nine patients (35 men and four women; median age, 60 years; six stage III and 33 stage IV) received CP on day 1 (100 mg/m2) followed by l FA (200 mg/m2/d x 5) plus FU (500 mg/m2/d x 5) administered by continuous venous infusion (three cycles planned). Mean plasma concentrations of FU, l FA, and 5-methyltetrahydrofolate (5MTHF) over the cycle were computed.. Clinical response was assessable for 33 patients. Response rates on the primary tumor site (n = 33) were 63.7% complete responses (CRs), 24.2% partial responses (PRs), and 12.1% treatment failures. Response rates on lymph nodes (n = 27) were 40.7% CRs, 37.1% PRs, and 22.2% treatment failures. The most frequent toxicity was mucositis (36.2% of cycles grade 3 to 4). Grade 3 to 4 nausea-vomiting, diarrhea, neutropenia, and thrombocytopenia occurred in 6.7%, 1.9%, 13.3%, and 1% of cycles, respectively. Pharmacokinetic analysis showed a wide interpatient variability for both FU (mean, 1.01 mumol/L; range, 0.16 to 2.09), l FA (mean, 1.89, mumol/L; range, 0.52 to 7.88) and 5MTHF plasma concentrations (mean, 3.85 mumol/L; range, 1.30 to 8.11). A significant correlation was demonstrated between FU concentration and hematologic toxicity grade, mucositis grade, and nausea-vomiting/diarrhea grade. Regarding tumor response, patients who failed to respond significantly exhibited lower FU and total folate concentrations than patients with a CR or PR.. This study highlights the efficacy of CP/FU/l FA in head and neck carcinoma and establishes the clinical importance of coupled FU/FA pharmacokinetics to predict pharmacodynamic variability.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Female; Fluorouracil; Humans; Hypopharyngeal Neoplasms; Laryngeal Neoplasms; Leucovorin; Male; Middle Aged; Nose Neoplasms; Oropharyngeal Neoplasms; Tetrahydrofolates

To evaluate the activity and toxicity of the drug combination cisplatin, fluorouracil by continuous infusion, and high-dose oral leucovorin calcium (PFL) as induction chemotherapy in patients with advanced and untreated squamous cell head and neck (SCHN) cancer.. Nonrandomized, prospective trial.. Referral center (comprehensive cancer center).. Twenty-two patients with stage III (n = 7) and IV (n = 15) M0 SCHN cancer of the larynx (n = 13), hypopharynx (n = 7), and oropharynx (n = 2) whose standard treatment would have required total laryngectomy.. Three cycles of PFL were administered prior to local-regional therapy (concomitant cisplatin and radiation and/or neck dissection, with total laryngectomy reserved for nonresponse or relapse). Chemotherapy included cisplatin (100 mg/m2) on day 1 by short intravenous infusion; fluorouracil (800 mg/m2) on days 1 through 5 by continuous infusion; and leucovorin (100 mg) every 4 hours by mouth for 30 doses. The PFL combination was administered every 21 days.. Clinical response to chemotherapy and observed toxic effects during chemotherapy.. Five patients were inevaluable for response, with three early deaths (infection in two and sudden death in one), one cerebrovascular accident, and one patient declining further chemotherapy. Of the remaining 17 patients, 10 had a major response to chemotherapy, but in only five patients (29%) was this complete (95% confidence interval, 8% to 51%). Other significant toxic effects included grade 3 to 4 mucositis in eight patients and grade 3 to 4 neutropenia in 10.. While PFL is active in patients with SCHN cancer, we were unable to reproduce the high complete response rates reported by other centers. Its use can be associated with significant toxic effects. We do not recommend the use of PFL for the treatment of patients with SCHN cancer outside the context of a clinical trial until there is further critical assessment of its activity and toxicity.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Fluorouracil; Humans; Laryngeal Neoplasms; Leucovorin; Middle Aged; Pharyngeal Neoplasms; Prospective Studies

Topics: Adult; Aged; Antineoplastic Agents; Bleomycin; Carcinoma, Squamous Cell; Cisplatin; Clinical Trials as Topic; Drug Administration Schedule; Drug Therapy, Combination; Female; Head and Neck Neoplasms; Humans; Laryngeal Neoplasms; Leucovorin; Male; Methotrexate; Middle Aged; Mouth Neoplasms; Pharyngeal Neoplasms

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Cisplatin; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Disease Progression; Drug Administration Schedule; Female; Humans; Induction Chemotherapy; Laryngeal Neoplasms; Leucovorin; Male; Middle Aged; Neoplasm Staging; Pharyngeal Neoplasms; Progression-Free Survival; Randomized Controlled Trials as Topic; Squamous Cell Carcinoma of Head and Neck; Tegafur; Time Factors; Young Adult

This regimen of concurrent chemoradiotherapy was safe and well tolerated. In terms of larynx preservation, the present regimen appears to be useful for patients with advanced resectable squamous cell carcinoma (SCC) of the larynx and hypopharynx.. To evaluate the efficacy and toxicity of concurrent chemoradiotherapy in patients with advanced resectable SCC of the larynx and hypopharynx, and to demonstrate the feasibility of larynx preservation.. Forty-six eligible patients were treated. The chemotherapy regimen consisted of a combination of four drugs: cisplatin (60 mg/m(2), day 4), 5-fluorouracil (5-FU) (600 mg/m(2) given continuously for 120 h, days 1-5), methotrexate (MTX) (30 mg/m(2), day 1), and leucovorin (LV) (20 mg/m(2), days 1-5). Two cycles of this regimen were given every 4 weeks during radiotherapy. Radiotherapy was delivered 5 days a week using a single daily fraction of 1.8-2.0 Gray, to a total dose of 66.6-70.2 Gray.. The 3-year disease-specific survival rates of patients with laryngeal or hypopharyngeal SCC were 81.3% and 78%, respectively. The 3-year disease-specific survival rates with larynx preservation of patients with laryngeal or hypopharyngeal SCC were 46.7% and 59%, respectively. The main toxicities were neutropenia, dermatitis, mucositis, and infection.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Cisplatin; Female; Fluorouracil; Humans; Hypopharynx; Laryngeal Neoplasms; Leucovorin; Male; Methotrexate; Middle Aged; Pharyngeal Neoplasms; Radiotherapy, Adjuvant; Survival Analysis; Treatment Outcome; Vitamin B Complex

The results of conventional radiotherapy in patients with inoperable recurrence of laryngeal cancer after total laryngectomy are bad. Therefore experimental methods including neutron therapy and combination of chemo- and radiotherapy have been used. This presentation evaluates results of different treatment modalities in patients with inoperable recurrences of laryngeal cancer after total laryngectomy.. Forty-two patients with inoperable recurrences of laryngeal cancer after total laryngectomy were treated. Thirty patients received radiotherapy alone, and 12 patients received multidrug chemotherapy and radiotherapy. Patients were irradiated with cobalt-60 beam, neutron beam and with mixed cobalt-60 and neutron beam. The tumor dose in cobalt-60 therapy was 60 Gy in 20 to 30 fractions. In 8 patients additional dose of 10 to 20 Gy in 5 to 10 fractions was given to the reduced field. The doses used in neutron irradiation varied from 10 to 13 Gy in 5 to 20 fractions.. In 20 patients (47.6%) complete regression after therapy was observed, but only 9 (21.4%) patients survived without evidence of disease at 2 years after radiotherapy. In patients treated with radiotherapy alone the 2-year disease-free survival was observed in 16.7% and in patients who received induction chemotherapy with Cisplatin followed by radical irradiation the 2-year disease-free survival was observed in 40%.. The results of therapy of inoperable recurrence of laryngeal cancer after total laryngectomy remain bad. Radiotherapy combined with multidrug chemotherapy including cisplatin may contribute to some improvement of the patients survival.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Cisplatin; Cobalt Radioisotopes; Combined Modality Therapy; Disease-Free Survival; Humans; Laryngeal Neoplasms; Laryngectomy; Leucovorin; Male; Methotrexate; Middle Aged; Neoplasm Recurrence, Local; Neutrons; Radiotherapy Dosage; Time Factors; Vincristine

A 62-year-old patient on long-term haemodialysis who developed an inoperable T2N3Mo squamous-cell carcinoma of the larynx was treated with weekly low-dose methotrexate (MTX) after failing to respond to radiotherapy. The patient was initially given one dose of 10 mg MTX (6 mg/m2) as a 1-h infusion, then he received three further i.v. doses of 20 mg (12 mg/m2). Haemodialysis was performed 15-18 h after each dose and the patient received folinic acid (30 mg i.v.q 6 h) until the MTX concentration was < 0.1 mumol/l. The MTX concentration was measured regularly until it reached < 0.1 mumol/l, and additional samples were withdrawn pre- and post-dialysis. The MTX elimination rate constant and half-life were estimated with the patient on and off dialysis. The patient failed to respond to treatment but did not experience MTX-related toxicity. The elimination half-life ranged from 22 to 42 h when he was off dialysis but fell to a median of 5.5 h during dialysis. Low-dose MTX was given to a patient on regular haemodialysis without evidence of toxicity. The rate of MTX elimination was increased during haemodialysis, although high MTX concentrations persisted for several days and prolonged rescue with folinic acid was required.

Topics: Antimetabolites, Antineoplastic; Area Under Curve; Carcinoma, Squamous Cell; Fatal Outcome; Humans; Infusions, Parenteral; Injections, Intravenous; Kidney Failure, Chronic; Laryngeal Neoplasms; Leucovorin; Male; Methotrexate; Middle Aged; Palliative Care; Renal Dialysis; Terminal Care

We evaluated the efficacy of folinic acid (Leucovorin, LV) on cell lethality induced by 5-fluorouracil (FU) alone or in combination with cisplatin (DDP) by using the HEp-2 laryngeal squamous carcinoma multicellular tumor spheroids (MTS) system. For LV, non-toxic concentration of 10(-5) M was used. For cells in the monolayer, 6 and 24 h exposure to LV increased FU-induced cell lethality approximately 7- and 2-fold, respectively, whereas LV did not influence the effect of FU for MTS. LV's lack of effect on cells in MTS may be interpreted to mean that LV cannot penetrate the MTS. For the monolayer, simultaneous exposure to 3 drugs, DDP, FU and LV, produced synergistic interaction. However, sequential exposures were marginally synergistic or antagonistic, irrespective of sequence of DDP first or last. In contrast, DDP followed by FU plus LV was most synergistic for MTS. Simultaneous exposure was also synergistic, however, FU plus LV followed by DDP was antagonistic. These results suggest that LV is unable to penetrate into the MTS core to potentiate FU activity. DDP appears to have enhanced LV penetration into the MTS core. The exploration of means to overcome limited penetration of LV appears important for successful treatment of head and neck carcinoma.

Topics: Carcinoma, Squamous Cell; Cell Count; Cell Death; Cisplatin; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Drug Screening Assays, Antitumor; Drug Synergism; Fluorouracil; Humans; Laryngeal Neoplasms; Leucovorin; Tumor Cells, Cultured

A patient with oat cell carcinoma of the larynx with metastasis to cervical lymph nodes is presented. Treatment with radiation and chemotherapy has achieved a sustained remission. Pretherapy staging and combined modality therapy are discussed.

Topics: Aged; Antineoplastic Agents; Carcinoma, Small Cell; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Humans; Laryngeal Neoplasms; Leucovorin; Lymphatic Metastasis; Male; Methotrexate; Neck; Radiotherapy Dosage; Remission, Spontaneous

Topics: Adult; Aged; Breast Neoplasms; Ear Neoplasms; Female; Humans; Injections, Intramuscular; Injections, Intravenous; Injections, Subcutaneous; Kinetics; Laryngeal Neoplasms; Leucovorin; Male; Methotrexate; Middle Aged; Nose Neoplasms; Remission, Spontaneous

Topics: Aged; Blood Platelets; Carcinoma, Squamous Cell; Female; Head; Head and Neck Neoplasms; Hematocrit; Hemoglobins; Humans; Laryngeal Neoplasms; Leucovorin; Leukocyte Count; Male; Methotrexate; Middle Aged

Topics: Adult; Aged; Anemia; Carcinoma, Squamous Cell; Cell Division; Drug Eruptions; Drug Synergism; Facial Neoplasms; Female; Head and Neck Neoplasms; Humans; Laryngeal Neoplasms; Leucovorin; Leukopenia; Lip Neoplasms; Male; Methotrexate; Middle Aged; Mouth Neoplasms; Mucous Membrane; Palatal Neoplasms; Pharyngeal Neoplasms; Tongue Neoplasms

Topics: Adenocarcinoma, Mucinous; Adult; Aged; Carcinoma, Squamous Cell; Female; Head and Neck Neoplasms; Humans; Infusions, Parenteral; Jaw Neoplasms; Laryngeal Neoplasms; Leucovorin; Leukopenia; Male; Methotrexate; Middle Aged; Mouth Neoplasms; Neoplasm Metastasis; Neoplasms; Paranasal Sinus Neoplasms; Pharyngeal Neoplasms; Salivary Glands; Thrombocytopenia; Tongue Neoplasms; Tonsillar Neoplasms

Topics: Carcinoma; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Geriatrics; Head and Neck Neoplasms; Humans; Infusions, Parenteral; Laryngeal Neoplasms; Leucovorin; Maxillary Neoplasms; Methotrexate; Nasopharyngeal Neoplasms; Neoplasm Metastasis; Neoplasms; Orbital Neoplasms; Palatal Neoplasms; Temporal Arteries; Tongue Neoplasms; Toxicology