Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To test the anti-tumour activity of rhizoxin in recurrent and/or metastatic squamous cell head and neck cancer, we performed a phase II study. Eligibility required histologically proven squamous cell head and neck cancer. Patients could only have received one prior chemotherapy. Patients were entered if WHO PS was < or = 2 and organ functions were normal. Treatment consisted of rhizoxin 1.5-2.0 mg m-2 i.v. bolus injection once every 3 weeks. Thirty-two patients entered the study. All were eligible, 31 were evaluable for toxicity and 25 for response. Toxicity mainly consisted of pain at the tumour site and leucocytopenia. Mild asthenia and stomatitis were also observed. Two objective partial responses, lasting 7.5 and 3.5 months, were seen. Rhizoxin at this dose and schedule has minor activity in recurrent and/or metastatic squamous cell head and neck cancer.
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PMID:Phase II study of rhizoxin in squamous cell head and neck cancer. The EORTC Early Clinical Trials Group. 856 50

Induction chemotherapy followed by radiation has been extensively studied in an effort to improve local control and possibly overall survival of patients with locally advanced head and neck cancer. From June 1989 until May 1991, 39 patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) were treated with 3 cycles of induction chemotherapy, consisting of cisplatin (100 mg/m2 d 1) and fluorouracil (1000 mg/m2 d 2-6) followed by radiation potentiated by weekly administration of carboplatin (60 mg/m2). Surgery was performed in selected patients with residual disease after the combined modality approach. Four cycles of adjuvant chemotherapy with carboplatin (325 mg/m2) and bleomycin (15 u) were administered in those patients who demonstrated a partial response after locoregional treatment. There were 36 men and 3 women with a median age of 56 (range 39-74) years and Karnofsky performance status of 70 (range 60-100). The primary site of the tumor was nasopharynx (8), oropharynx (8), hypopharynx (3), oral cavity (4), larynx (13), paranasal sinus (2), and salivary glands (1). Thirty-two (82%) patients presented with stage IV disease. After the completion of induction chemotherapy, 14 (36%, 95% CI 21-53%) patients achieved a complete response (CR). This CR rate was increased to 56% (95% CI, 42-74%) after locoregional treatment. Main toxicities included nausea/vomiting (56%), leukopenia (40%), anemia (30%), thrombocytopenia (10%), stomatitis (28%), diarrhea (17%), and alopecia (12%). Median relapse-free survival was 18 (1-50) months, median time to progression was 13 (0.3-58.5) months, and median survival 19 (0.3-59) months. Induction chemotherapy with cisplatin and fluorouracil followed by radiation potentiated with carboplatin is feasible. However, this combined modality approach, as applied in the present study, does not appear to yield superior results than those reported with chemotherapy followed by radiation alone.
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PMID:Cisplatin and continuous infusion of fluorouracil followed by radiation and weekly carboplatin in the treatment of locally advanced head and neck cancer: a Hellenic Cooperative Oncology Group study. 863 Jun 90

A priming dose of 5-fluorouracil can decrease the toxicity and retain the efficacy of high-dose methotrexate in laboratory models. This Phase I study determined the maximum tolerated dose of methotrexate that can be administered after a dose of 5-fluorouracil without leucovorin rescue. Forty-two patients received 5-fluorouracil (500 mg/m2) by bolus injection followed in 2 h by methotrexate infused over 1 h; treatment was repeated every 3 weeks. Patients received five doses of leucovorin (10 mg/m2 every 6 h); this was reduced to two doses and then to zero doses (no rescue) if less than grade 2 toxicity occurred in prior treatments. If safe, at least two patients received no leucovorin rescue with their first treatment. The dose of methotrexate was escalated in cohorts of patients, starting with a methotrexate dose of 200 mg/m2. Previously untreated patients maximally tolerated 1600 mg/m2 of methotrexate with 5-fluorouracil pretreatment. Leukopenia combined with stomatitis prevented deescalation of leucovorin doses. Fourteen percent of total courses and 15% of courses without leucovorin rescue resulted in dose limiting toxicity. MTX levels exceeded levels that require leucovorin rescue. Four of the 33 (12%) advanced head and neck cancer patients had objective responses to therapy; median survival was 10 months. Previously treated patients were less tolerant; oral and hematological toxicities were troublesome; 400 mg/m2 of methotrexate was the approximate maximum tolerated dose. Forty-seven percent of total courses and 60% of courses without leucovorin rescue resulted in dose limiting toxicity. There were no responses. Although the antineoplastic activity is poor, prior 5-fluorouracil exposure does protect tissues susceptible to methotrexate toxicity.
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PMID:A phase I study of methotrexate administration following 5-fluorouracil. 882 78

Advances in vascular radiology techniques for superselective transfemoral arterial infusion prompted us to evaluate the effects of high-dose rapid regional carboplatin infusion for patients with advanced head and neck squamous cell carcinomas. Twenty untreated patients received three infusions of carboplatin (300-350 mg/m2) every 2 weeks with this method. All the infusions were performed without any complication. Treatment was well tolerated, with moderate (Grade 1-3 WHO) local toxicity (stomatitis, dermatitis and alopecia) and minimal (Grade 1-2 WHO) myelosuppression. The total response index (complete response plus partial response) was 94% for primary tumors and 50% for neck metastases. Neoadjuvant chemotherapy employing superselective rapid infusion of high-dose carboplatin is a feasible, relatively nontoxic, effective technique and may have important applications in multimodality therapy of untreated patients with advanced head and neck cancer.
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PMID:[High-dose carboplatin superselective intraarterial chemotherapy in advanced head and neck cancer]. 898 37

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) appears to be one of the most active drugs in the treatment of advanced head and neck cancer. The maximum tolerated dose of paclitaxel in combination with carboplatin is currently being evaluated in phase I/II studies. We designed a phase II study to evaluate the activity and acute and cumulative toxicity of this combination in patients with recurrent or metastatic cancer of the head and neck. Chemotherapy consisted of paclitaxel 200 mg/m2, given as a 3-hour infusion, and carboplatin dosed to an area under the concentration-time curve of 7 mg x min/mL, administered every 28 days. Granulocyte colony-stimulating factor (5 microg/kg) also was given on days 2 to 12 of each cycle. At the time of this report, 41 patients had entered this study. Primary sites included the nasopharynx (10 patients), larynx (18), oral cavity (three), oropharynx (six), hypopharynx (three), and unknown (one). Among 25 evaluable patients with non-nasopharyngeal cancer, there were two complete responses and three partial responses, for an overall response rate of 20% (95% confidence interval, 4% to 36%). Among eight evaluable patients with nasopharyngeal cancer, four achieved a complete response and two a partial response. Grade 3 to 4 toxicities included anemia (2.5%), leukopenia (7.5%), thrombocytopenia (5%), vomiting (5%), stomatitis (2.5%), and infection (5%). These preliminary data indicate that the combination of paclitaxel and carboplatin is active against advanced head and neck cancer, particularly when used in the treatment of nasopharyngeal cancer.
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PMID:Paclitaxel and carboplatin in recurrent or metastatic head and neck cancer: a phase II study. 904 40

Phase II study of nedaplatin (NDP), a new derivative of cisplatin, was completed in 1990, so this agent is now commercially available. NDP is very effective for head and neck cancer. Out of the 90 evaluable patients, CR was achieved in 11 patients and PR in 27 with a response rate of 42%. A new combination chemotherapy containing NDP, especially NDP + 5-FU, was clinically tried. Furthermore concurrent NDP and radiotherapy will be tried in the near future. Phase II study of S-1 (tegafur + CDHP + Oxo) and taxotere (TXT), however, is ongoing. The results obtained so far are almost satisfactory. The aouthor also adopted several new agents which were presented at the ASCO meeting (1993-1997): taxol (TXL), taxotere (TXT), topotecan, amonafide, vinorelbine and thymitaq. Response rates of these agents were as follows: TXL: 26-37%, TXT: 27-41%, topotecan: 0-27%, vinorelbine: 6.7-12.5%, thymitaq: 18.2% and amonafide: 3.6%. So TXL and TXT are very effective for head and neck cancer. In terms of combination chemotherapy, response rates are 33-71% in TXL + CDDP, 23-62% in TXL + CBDCA, 78% in TXT + CDDP and 75% in TXT + CDDP + 5-FU. Concurrent radiotherapy and chemotherapy including new agents are interesting and important issues. Two kinds of protocol were adopted, 5-FU + HU + TXL + RT and TXL + CBDCA + RT. Both protocols are responsive to squamous cell carcinoma of the head and neck. But severe local toxicity (stomatitis) and bone marrow suppression pose problems.
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PMID:[Head and neck cancer]. 935 Feb 34

We performed a phase II study to evaluate the activity and toxicity of the combination of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and carboplatin as first-line treatment in patients with recurrent or metastatic head and neck cancer. From March 1994 until August 1996, 49 patients were treated with paclitaxel 200 mg/m2 by 3-hour infusion followed by carboplatin at an area under the concentration-time curve of 7 mg/mL x min; treatment was requested every 4 weeks. Granulocyte colony-stimulating factor was administered prophylactically on days 2 to 12 of each cycle. The study included 41 men and eight women, with a median age of 57 years (range, 23 to 73 years). Most of the patients were symptomatic and had locoregional disease. Primary sites included nasopharynx (14 patients), oropharynx (six), oral cavity (four), hypopharynx (three), larynx (20), paranasal sinuses (one), and unknown (one). After the completion of treatment, four patients (8%; 95% confidence interval, 0% to 16%) achieved a complete response and 12 (24%; 95% confidence interval, 12% to 37%) achieved a partial response. Grade 3/4 toxicities included anemia (2%) and leukopenia, thrombocytopenia, nausea/vomiting, diarrhea, and stomatitis (4% each). After a median follow-up of 15.3 months, median time to progression was 5.7 months (range, 0.5 to 29.8+ months) and median survival was 13.3 months (range, 0.5 to 30.2+ months). In our ongoing study in a similar patient population, gemcitabine was substituted for carboplatin.
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PMID:Paclitaxel in combination with carboplatin or gemcitabine for the treatment of advanced head and neck cancer. 942 62

In developing new anticancer agents, the most important thing is the balancing of antitumor activity and toxicity. To achieve high activity and low toxicity, S-1 was designed, in which tegafur, prodrug of 5-FU, was combined with two classes of modulators. CDHP, inhibitor of 5-FU degradation in liver and Oxo, inhibitor of 5-FU phosphoribosylation in digestive tract, respectively. This cooperative study with 15 nation-wide institutes was conducted to evaluate the antitumor activity and toxicity of S-1 in patients with advanced head and neck cancer from Jan. 1994 to March 1996 in Japan. Out of 26 patients, CR was achieved in 1 and PR in 11 with a response rate of 46.2%, while adverse events of grade 3 were as follows: hemoglobinemia (7.7%), leukocytopenia, neutropenia, stomatitis and anorexia (3.8%), each. Neither grade 4 adverse event nor treatment-related deaths were observed. Based on these findings, it was concluded that S-1 is a useful anticancer agent with the low grade toxicities for treatment of the patients with advanced head and neck cancer, and the effects of CDHP and Oxo found in preclinical studies might be also reflected in these results.
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PMID:[Early phase II study of S-1 in patients with advanced head and neck cancer. S-1 Cooperative Study Group (Head and Neck Working Group)]. 967 77

We describe in this paper a therapeutic modality which is based on a self-rescuing concept (SRC) featuring dual activity, i.e., effect-enhancing activity and adverse reaction-reducing activity. We present the theory and practice of S-1, a novel oral fluoropyrimidine anticancer agent designed to enhance anticancer activity and reduce gastrointestinal toxicity through the deliberate combination of the following components: an oral fluoropyrimidine agent, tegafur (FT); a DPD inhibitor (CDHP: 5-chloro-2, 4-dihydroxypyridine) which is about 200-fold more potent than uracil used in UFT; and an ORTC inhibitor (Oxo: potassium oxonate) which is localized in the gastrointestinal tract. We devised a novel oral anticancer agent, S-1, as a combination drug with a molar ratio of 1:0.4:1 for FT, CDHP, and Oxo, respectively. To compare S-1, FT, and UFT in terms of their anticancer activity and adverse reactions, a colon cancer implantation model in rats was used for 4-week consecutive oral administration from the time when the postimplantation tumor weight become about 2 g. The tumor disappeared on day 16 at a given dose of S-1 (as 22.5 mg/kg FT), and the tumor did not reappear for at least three months. Antitumor activity was more marked with S-1 than FT and UFT. Adverse reaction, i.e., stomatitis, depilation, and weight loss, were less frequent in the S-1 group than in the other groups. A clinical pharmacology study examined blood concentrations of 5-FU after twice-a-day administration after meals of S-1 at a dose of 40 mg/m2. Blood concentrations of 5-FU were 60 to 200 ng/ml in all twelve patients examined. Late phase II clinical trials of S-1 were conducted in patients with advanced and recurrent stomach cancers, in the same regimen as for the clinical pharmacology study. It basically consisted in four cycles, each of which comprised 4-week, twice-a-day, consecutive oral administration with a 2-week withdrawal. The overall response rate was 44.6% (45/101). Median survival time (MST) was 224 days. S-1 was given manufacturing approval by the Ministry of Health and Welfare of Japan after a priority review, with indications for advanced and recurrent stomach cancers. A late phase II clinical study of S-1 in patients with advanced/recurrent head and neck cancer was conducted in 59 eligible patients. Objective responses were 4 complete response (CR) and 13 partial response (PR), for a response rate of 28.8% (17/59). MST was 344 days. Grade 4 hemoglobin decrease was observed in one case; however, this returned to normal after the termination of drug administration and blood transfusion. Therefore, this event was confirmed to be reversible. A late phase II clinical trial of S-1 was conducted to evaluate the efficacy and toxicities in patients with metastatic colorectal carcinoma. Sixty-three patients with measurable metastatic colorectal carcinoma were enrolled in this clinical trial. The overall response rate was 35.5% (22/62), and the MST was 378 days. The main adverse reactions were myelosuppression and GI toxicities. The incidence of neutropenia (Grade 3 or 4) was 13%, while the incidence of other adverse reactions was 10% or below. None of 53 outpatients required to be hospitalization due to adverse reactions. Late phase II clinical trials of S-1 are in progress for colorectal cancer, breast cancer and non-small cell lung cancer. To establish the standard therapeutic modality for cancers, including gastrointestinal cancers, in Japan, the conduction of clinical trials combining S-1 and other anticancer drugs holds promise for the future.
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PMID:[New oral anticancer drug, TS-1 (S-1)--from bench to clinic]. 1143 58

Access to the stomach for long-term enteral feeding or decompression can be achieved with numerous methods. The methods include laparotomy, gastroscopy, laparoscopy, and fluoroscopy. All methods have been shown to be safe and effective. Percutaneous endoscopic gastrostomy (PEG) was introduced by Ponsky in 1990, and laparoscopic gastrostomy was introduced 10 years later. PEG rapidly replaced open gastrostomy as the method of choice for enteral nutrition. The laparoscopic alternative was ideal for patients who were not candidates for PEG placement. The laparoscopic or laparoendoscopic placement of enteral tubes allows visualization of the intestinal tract to ensure proper tube positioning. Many patients are not candidates for a PEG because of head and neck cancer, esophageal obstruction from stricture or carcinoma, large hiatal hernia, gastric volvulus, overlying intestine or liver, facial trauma with wired mandible, or severe stomatitis secondary to radiation therapy. Lastly, laparoscopy lessens the chance of injury to the surrounding structures, adhesions can be safely lysed, and metastatic or concomitant disease may be identified. This report will review the numerous methods available to the laparoscopic surgeon for gaining access to the stomach or intestine.
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PMID:Laparoendoscopic approaches to enteral access. 1158 70


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