levoleucovorin and Hypopharyngeal-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

Forty-one patients with locally advanced hypopharyngeal carcinomas were followed for at least 3 years (median, 60 months) after simultaneous radiochemotherapy. Conventionally fractionated radiotherapy was administered as 5 x 2 Gy/week to a total dose of 30 Gy within 3 weeks. From the fourth week an accelerated hyperfractionated schedule was used as 2 x 1.4 Gy/day five days weekly given exclusively to the first order target volume of macroscopic tumor (adding up to a total dose of 72 Gy in six weeks). The second and third order target volumes received conventional fractionation only to 60 Gy and 50 Gy, respectively. The moderate acceleration of the concomitant boost scheme in the second half was counterbalanced during the first week by the introduction of a 5-fluorouracil bolus of 350 mg/M2 with 200 mg/M2 folinic acid and a subsequent continuous infusion using the same dose each 24 h for 5 days. Additionally, a Mitomycin-C bolus of 10 mg/M2 was infused at the fifth day and on the first day of the sixth week. Six weeks after treatment the patients were restaged. In cases with residual carcinoma salvage surgery was performed (11 patients). Late effects of therapy were analyzed according to the Lent-Soma index and life quality according to the European Organisation for Research and Treatment of Cancer-Module. Late effects of treatment were tolerable and were controlled locally. The 3-year-survival rate was 39%, with a local-regional recurrence-free control rate of 71%. Fifty-two percent of all cases of death were caused by distant metastases, secondary carcinomas or other diseases not related to tumor recurrence. The poor prognosis of hypopharyngeal carcinomas despite acceptable local tumor control may be due to specific biological factors present in affected patients.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Combined Modality Therapy; Dose Fractionation, Radiation; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fluorouracil; Follow-Up Studies; Humans; Hypopharyngeal Neoplasms; Leucovorin; Male; Middle Aged; Mitomycin; Neoplasm Staging; Radiotherapy, Adjuvant; Survival Rate

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

The aim of this study was to evaluate treatment results in our hypopharyngeal cancer patients.. A total of three hundred and ninety five hypopharyngeal cancer patients received radical treatment at our hospital; 96% were male. The majority were habitual smokers (88%), alcohol drinkers (73%) and/or betel quid chewers (51%). All patients received a CT scan or MRI for tumor staging before treatment. The stage distribution was stage I: 2 (0.5%); stage II: 22 (5.6%); stage III: 57 (14.4%) and stage IV: 314 (79.5%). Radical surgery was used first in 81 patients (20.5%), and the remaining patients (79.5%) received organ preservation-intended treatment (OPIT). In the OPIT group, 46 patients received radiotherapy alone, 156 patients received chemotherapy followed by radiotherapy (CT/RT) and 112 patients received concomitant chemo-radiotherapy (CCRT).. The five-year overall survival rates for stages I/II, III and IV were 49.5%, 47.4% and 18.6%, respectively. There was no significant difference in overall and disease-specific survival rates between patients who received radical surgery first and those who received OPIT. In the OPIT group, CCRT tended to preserve the larynx better (p = 0.088), with three-year larynx preservation rates of 44.8% for CCRT and 27.2% for CT/RT. Thirty-seven patients developed a second malignancy, with an annual incidence of 4.6%.. There was no survival difference between OPIT and radical surgery in hypopharyngeal cancer patients at our hospital. CCRT may offer better laryngeal preservation than RT alone or CT/RT. However, prospective studies are still needed to confirm this finding. Additionally, second primary cancers are another important issue for hypopharyngeal cancer management.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Digestive System Surgical Procedures; Female; Humans; Hypopharyngeal Neoplasms; Incidence; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Neoplasm Staging; Neoplasms, Second Primary; Radiotherapy; Taiwan; Tegafur; Young Adult

We treated a patient with hypopharyngeal carcinoma who achieved a complete response following three cycles of chemotherapy with docetaxel, cisplatin, 5-FU and levofolinate. A 77-year-old Japanese male with hypopharyngeal carcinoma had undergone a radical esophageal operation and subsequent radiation therapy in the lower neck and upper mediastinum in 1991 because of esophageal carcinoma. He refused radical total laryngopharyngotomy, and agreed to chemotherapy. Three cycles of chemotherapy with docetaxel, CDDP, 5-FU and l-LV were then administered and no other therapy was given. Sixteen months after this chemotherapy he had no recurrence and no metastasis. We conclude that chemotherapy using docetaxel, cisplatin, 5-FU, and levofolinate will be useful for treating head and neck cancer.

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