levoleucovorin and Deglutition-Disorders

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Deglutition Disorders; Esophageal Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Palliative Care; Radiation Dose Hypofractionation; Treatment Outcome

Cisplatin (P) and 5-fluorouracil (5FU) have demonstrated activity for the treatment of squamous cell carcinoma of the esophagus. Previous studies have shown that leucovorin (L) may potentiate the antitumoral activity of 5FU, so we tested the combination P-5FU-L in 31 patients with inoperable squamous cell esophageal carcinoma. Chemotherapy consisted of P 20 mg/m2 in 4 h, followed by L 200 mg/m2 in 2 h and 5FU 600 mg/m2 in 18 h. This schedule was repeated for 5 days every 4 weeks. The treatment plan included three courses of chemotherapy followed by radiotherapy. The overall response rate was 58% (95% CI = 39-76%), with one complete remission (3%), and 61% of patients reported an improvement in dysphagia. Gastrointestinal toxicity was the main side effect: grade 3-4 mucositis appeared in 19% of patients, grade 3-4 nausea/vomiting in 13%, and grade 3-4 diarrhea in 6.5%. There was one toxic death caused by neutropenia and sepsis. Nineteen patients received local radiotherapy after chemotherapy, which increased the overall response rate to 63% (5% complete responses). Dysphagia improved in 75% of them. The median survival for all patients was 11 months. This study shows that sequential therapy with P-5FU-L and radiotherapy achieves a high response rate as well as adequate symptomatic relief in patients with inoperable esophageal cancer. The results justify further evaluation of P-5FU-L in patients with earlier-stage disease.

Topics: Adult; Aged; Antidotes; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Deglutition Disorders; Diarrhea; Drug Administration Schedule; Drug Synergism; Enzyme Inhibitors; Esophageal Neoplasms; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Mucous Membrane; Nausea; Radiotherapy, Adjuvant; Remission Induction; Survival Rate; Thymidylate Synthase; Vomiting

Neoadjuvant chemotherapy is an accepted standard for locally advanced esophagogastric junction adenocarcinoma. However, the dysphagia frequently associated with this condition may interfere with patient tolerance of this treatment. In many centers, invasive tube feeding, placed either endoscopically, radiographically, or surgically, is used to address this issue, but it can cause significant morbidity. We sought to determine if an approach of goal-directed dietary counseling and appropriately timed neoadjuvant chemotherapy could obviate the need for invasive tube feeding.. Patients with locally advanced (cT3 or N+) esophageal and esophagogastric junction adenocarcinoma undergoing neoadjuvant TCF [Taxotere, cisplatin 5-fluorouracil (5-FU)], ECF (epirubicin, cisplatin, 5-FU), or FLOT (docetaxel, oxaliplatin, leucovorin, and 5-FU) at the McGill University Health Center from March 2007 to September 2012 were identified from a prospective database. All received individualized goal-directed dietary counseling, were monitored for signs/symptoms of malnutrition with serial (baseline/presurgery) body mass index, albumin, and completed serial symptom scores (dysphagia), and quality-of-life questionnaires (Functional Assessment in Cancer Therapy with the esophageal subset, FACT-E). We assessed the response of dysphagia and nutritional status to neoadjuvant chemotherapy and the need for invasive tube feeding.. Of 130 patients undergoing neoadjuvant chemotherapy, 78 had severe dysphagia (defined as dysphagia score ≥2 on a 5-point Likert scale), most of whom received TCF (91 %). Overall dysphagia scores improved in 75 (96 %) of 78 patients from a dysphagia score of 3-0, most of which improved after the first cycle of therapy. This was associated with an increase in quality of life (FACT-E scores 117 ± 23 to 140 ± 20). With maintenance of weight (70 ± 22 to 69 ± 24 kg), body mass index (24.5 ± 8 to 23.9 ± 7 kg/m(2)), and serum albumin (40 ± 5 to 37 ± 4 g/L). Only one patient required a stent, and none required jejunostomy or gastrostomy.. Appropriately timed neoadjuvant chemotherapy with a highly effective regimen rapidly restores normal swallowing, maintains nutritional status, and obviates the need for invasive tube feeding in patients with significant dysphagia from esophageal adenocarcinoma.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Deglutition Disorders; Docetaxel; Enteral Nutrition; Epirubicin; Esophageal Neoplasms; Esophagogastric Junction; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Prognosis; Prospective Studies; Quality of Life; Taxoids

To compare chemotherapy first (group 1) versus self-expanding metal stent first (group 2) for the management of malignant dysphagia in unresectable oesophageal or gastro-oesophageal junction cancer.. Patients from two university hospitals with severe malignant dysphagia (dysphagia score ≥ 2) uneligible for surgery or radiochemotherapy were evaluated retrospectively.. Forty-two patients were included in group 1, and 29 in group 2. After 4 weeks, dysphagia scores improved by at least 1 point in 67% of patients in group 1 versus 93% in group 2 (p=0.01); 48% of patients in group 1 were able to eat solid food versus 68% in group 2 (p=0.054). In group 1, a self-expanding metal stent was secondarily placed in 18 patients (42.9%), whereas in group 2 dysphagia required a second self-expanding metal stent placement in 33.3% of patients.. Chemotherapy as the first treatment may be a valid option, avoiding self-expanding metal stent insertion in half of the patients.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Deglutition Disorders; Endoscopy, Gastrointestinal; Esophageal Neoplasms; Esophageal Stenosis; Esophagogastric Junction; Esophagoscopy; Female; Fluorouracil; Gastroscopy; Humans; Leucovorin; Male; Metals; Middle Aged; Organoplatinum Compounds; Palliative Care; Quality of Life; Retrospective Studies; Severity of Illness Index; Stents

Peripheral, acute or chronic, neurotoxicity is one of the main dose-limiting adverse effects of oxaliplatin (OXA). Acute neurotoxicity is typically characterized by distal and perioral cold-induced paresthesias and dysesthesias, but other uncommon symptoms might also be present.. The aim of this post hoc analysis of data extracted from a prospective, multicenter study was to assess the incidence of uncommon acute OXA neurotoxicity symptoms in patients undergoing OXA-based chemotherapy.. One hundred chemotherapy-naïve patients (62 males, 38 females, aged 64.7 ± 8.7 years) with colorectal cancer scheduled to receive OXA-based therapy (FOLFOX-4, FOLFOX-6, and XELOX) underwent neurologic evaluation after the 1st infusion and then after 3 and 6 months of OXA-based chemotherapy (after 6th or 4th and 12th or 8th cycles, respectively, according to regimen). At evaluation, patients were asked to report the presence and characteristics of acute hyperexcitability symptoms.. Eighty-two patients presented typical symptoms of acute OXA neurotoxicity in the form of cold-induced paresthesias and dysesthesias. In 45/82 (54.9 %) of patients, uncommon symptoms were also present; shortness of breath (32 %), jaw spasm (26 %), fasciculations (25 %), cramps (20 %), and difficulty in swallowing (18 %) were more frequently reported, while voice (4 %) and visual changes, ptosis and pseudolaryngospasm (1 %) occurred rarely. No significant correlation was disclosed between acute OXA neurotoxicity and chemotherapy regimen, cumulative dose of OXA or patients' age.. A high percentage of patients treated with OXA-based chemotherapy develop acute neurotoxicity also with uncommon manifestations. Since OXA acute neurotoxicity might be related to the onset of chronic neurotoxicity, these patients should be closely monitored to avoid this dose-limiting adverse effect.

Topics: Acute Disease; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Colorectal Neoplasms; Deglutition Disorders; Deoxycytidine; Drug Administration Schedule; Dyspnea; Female; Fluorouracil; Humans; Incidence; Leucovorin; Male; Middle Aged; Neurotoxicity Syndromes; Organoplatinum Compounds; Oxaliplatin; Oxaloacetates; Paresthesia; Prospective Studies; Spasm

Topics: Adult; Aged; Anaphylaxis; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Deglutition Disorders; Deoxycytidine; Dyspnea; Female; Fluorouracil; Hoarseness; Humans; Hypokalemia; Incidence; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Oxaloacetates; Prospective Studies; Respiratory Sounds; Sex Factors

The purpose of this study was to evaluate the efficacy and toxicity of an induction chemotherapy schedule followed by high-dose radiotherapy and concurrent chemotherapy for locally advanced squamous cell carcinomas of the upper and midthoracic esophagus. Patients were treated with three courses of fluorouracil, leucovorin, etoposide, and cisplatin-containing induction chemotherapy followed by high-dose external beam radiotherapy to 65 Gy in 6 weeks for T4 and obstructing T3 tumors. Transversable T3 tumors received 60 Gy in 6 weeks by external radiotherapy, followed by two high-dose-rate esophageal brachytherapy fractions of 4 Gy in 5-mm tissue depth. Concurrent to radiotherapy, cisplatin and etoposide were given. Long-term survival of 22 patients was 41% and 31% at 2 and 3 years, respectively, with a median follow-up of 39 months. The probability of locoregional tumor recurrence was 60% at 3 years for all patients and 30% for those with a partial or complete response to induction chemotherapy. Acute toxicity of this schedule was moderate. Long-term survivors had a good swallowing function. This schedule offers a considerable chance of long-term survival for patients with locally advanced squamous cell carcinomas of the upper and midthoracic esophagus. Local in-field recurrences are the main risk after definitive radiochemotherapy. Dose escalation of radiotherapy is possible because of the observed low late toxicity.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Brachytherapy; Carcinoma, Squamous Cell; Cisplatin; Cohort Studies; Combined Modality Therapy; Deglutition Disorders; Drug Administration Schedule; Esophageal Neoplasms; Etoposide; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Prognosis; Quality of Life; Survival Analysis