levoleucovorin and Oropharyngeal-Neoplasms

We evaluated the efficacy and toxicity of cisplatin, tegafur plus uracil and leucovorin as neoadjuvant chemotherapy for locally advanced squamous cell carcinoma (SCC) of the oropharynx and hypopharynx. Forty-six patients (stage IV, 83%; N2/3, 52%) were treated with PUL (50 mg/m2 cisplatin on day 1, 300 mg/m2 tegafur plus uracil orally and 60 mg leucovorin orally on days 1-14) over a 14-day cycle. Evaluation after 3 cycles led to chemotherapy termination if primary tumor responses were less than partial responses. Otherwise, PUL was continued up to 6 cycles before locoregional therapy. Patients achieving at least good partial responses at the primary site after neoadjuvant chemotherapy received radiotherapy for organ preservation. Chemotherapy responses were analyzed by intent-to-treat. Response rates of primary sites were 71.7% (33 of 46) with 34.8% (16 of 46) showing a complete response. Thirty patients (65.2%) achieved good partial responses at the primary site. Overall response and complete response rates of neck lymph nodes were 68.6% (24 of 35) and 25.7% (nine of 35). The combined response rate of primary site and neck lymph nodes was 63% (95% confidence interval 48.5-77.5%) with a complete response rate of 15.2%. Toxicities of WHO grade 3-4 included anemia (19.6%), diarrhea (17.4%) and neutropenia (8.7%). With a median follow-up of 36 months, overall survival and disease-free survival rates were 45.7% (21 of 46) and 41.3% (19 of 46); organ preservation rate was 90% (19 of 21). We concluded that the outpatient PUL regimen was a moderately effective, less-toxic neoadjuvant chemotherapy for SCC of the oropharynx and hypopharynx. PUL should be studied further with other active agents or radiotherapy.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Female; Humans; Hypopharyngeal Neoplasms; Leucovorin; Male; Maximum Tolerated Dose; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Oropharyngeal Neoplasms; Survival Rate; Tegafur; Uracil

We designed two sequential trials of induction chemotherapy followed by definitive radiation in patients with potentially resectable head and neck cancer to determine whether organ preservation is feasible without apparent compromise of survival Study Design Both trials were Phase II studies.. Two clinical trials were conducted sequentially at the University of Michigan. Fifty-two patients enrolled in the first study and were treated with a planned three cycles of carboplatin and 5-fluorouracil. Patients who achieved at least 50% reduction in the size of the primary tumor received definitive radiation therapy, to a dose of 6600 to 7380 cGy. Patients with minimal response or progression had immediate salvage surgery. Thirty-seven patients enrolled in the second trial, in which the chemotherapy consisted of carboplatin, 5-fluororuracil, and leukovorin. Responders were treated with accelerated radiation therapy, to a total dose of 7120 cGy delivered in 41 fractions over 5.5 weeks.. Toxicity and response were similar in both trials; therefore, the results are reported first separately and then combined for all 89 patients. Tumor sites included: oropharynx, 55 patients; hypopharynx, 34 patients. Eighty-three percent of patients tolerated all three cycles of chemotherapy and toxicity was mild. Response to chemotherapy was: 48% complete response at the primary tumor site, and 34% partial response at the primary tumor site. Initial organ preservation at individual tumor sites was: oropharynx, 58%; hypopharynx, 59%. Median survival was 28 months, and survival at 3 and 5 years was 40% and 24%, respectively.. These two regimens were well tolerated, and survival did not appear to be compromised by organ preservation treatment compared with historical controls. This approach warrants further investigation, particularly in those patients for whom surgery could be functionally debilitating.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Carboplatin; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Disease-Free Survival; Female; Fluorouracil; Humans; Hypopharyngeal Neoplasms; Leucovorin; Male; Middle Aged; Oropharyngeal Neoplasms; Radiotherapy Dosage; Survival Analysis

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 review the experience with and evaluate the treatment plan for helical tomotherapy for the treatment of oropharyngeal cancer.. Between November 1, 2006 and January 31, 2009, 10 histologically confirmed oropharyngeal cancer patients were enrolled. All patients received definitive concurrent chemoradiation with helical tomotherapy. The prescription dose to the gross tumor planning target volume, the high-risk subclinical area, and the low-risk subclinical area was 70 Gy, 63 Gy, and 56 Gy, respectively. During radiotherapy, all patients were treated with cisplatin, 30 mg/m(2), plus 5-fluorouracil (425 mg/m(2))/leucovorin (30 mg/m(2)) intravenously weekly. Toxicity of treatment was scored according to the Common Terminology Criteria for Adverse Events, version 3.0. Several parameters, including maximal or median dose to critical organs, uniformity index, and conformal index, were evaluated from dose-volume histograms.. The mean survival was 18 months (range, 7-22 months). The actuarial overall survival, disease-free survival, locoregional control, and distant metastasis-free rates at 18 months were 67%, 70%, 80%, and 100%, respectively. The average for uniformity index and conformal index was 1.05 and 1.26, respectively. The mean of median dose for right side and left side parotid glands was 23.5 and 23.9 Gy, respectively. No Grade 3 toxicity for dermatitis and body weight loss and only one instance of Grade 3 mucositis were noted.. Helical tomotherapy achieved encouraging clinical outcomes in patients with oropharyngeal carcinoma. Treatment toxicity was acceptable, even in the setting of concurrent chemotherapy. Long-term follow-up is needed to confirm these preliminary findings.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Disease-Free Survival; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Oropharyngeal Neoplasms; Parotid Gland; Radiodermatitis; Radiotherapy Dosage; Radiotherapy, Intensity-Modulated; Stomatitis; Tumor Burden

We encountered a patient with metastatic disease of the lung from oropharyngeal cancer who achieved a complete response to 3 cycles of chemotherapy with docetaxel, cisplatin, 5-FU and l-leucovorin (TPFL). A 72-year-old man was found to have metastatic disease of the lung 32 months after treatment of oropharyngeal squamous cell carcinoma. Chemotherapy was initiated with TPFL and the patient obtained a complete response after 3 cycles. Twelve months after chemotherapy he had no recurrence. We conclude that the use of docetaxel cisplatin, 5-FU and l-leucovorin for metastatic squamous cell carcinoma of the head and neck is a viable option.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Docetaxel; Drug Administration Schedule; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Male; Oropharyngeal Neoplasms; Remission Induction; Taxoids

A cytomorphic, stereological study was made by computerized image analysis of six nuclear morphometric variables and one stereological nuclear variable. Variables were measured on 150 randomly selected tumor cells in oropharyngeal biopsies from 44 patients with oropharyngeal cancer who had not responded completely to induction chemotherapy. The nuclei of tumoral cells were larger (mean nuclear area, perimeter, and volume), more rounded, and had a less irregular nuclear contour index.

Topics: Adult; Aged; Antineoplastic Agents; Carcinoma, Squamous Cell; Cisplatin; Fluorouracil; Humans; Immunosuppressive Agents; Leucovorin; Male; Middle Aged; Oropharyngeal Neoplasms; Oropharynx; Retrospective Studies