Search PubMed⌕ Search

Biomedical subjects

D Kelsen

Publications and source records attributed to D Kelsen.

At least 73 records · Page 4Linked to original sources
PubMed1985

Carboplatin: a new platinum analog in the treatment of epidermoid carcinoma of the esophagus.

Thirty-one patients with advanced epidermoid carcinoma of the esophagus were treated with carboplatin (CBDCA), a second-generation cisplatin analog. Thirty patients were evaluable for response. Major responses (complete response) were seen in two patients (7%; 95% confidence limits, 1%-20%). The median survival from initiation of the protocol was 3 months (range, 0.1-16). Neither renal dysfunction nor emesis was a significant problem with CBDCA; hematologic toxicity was dose-limiting. Thrombocytopenia was more marked than leukopenia. CBDCA is a well-tolerated cisplatin analog that produced two complete responses in patients with advanced epidermoid carcinoma of the esophagus, where such responses are rarely observed. Although the observed response rate was only 7%, the 95% confidence limits overlap those previously reported for cisplatin (12%-31%).

Adult↗
PubMed1985

Phase II trial of high-dose cisplatin in patients with malignant mesothelioma.

Twenty-five patients with advanced malignant mesothelioma were treated in a phase II trial with high-dose cisplatin (DDP). All patients had measurable or evaluable disease. Seven patients had received prior chemotherapy. DDP (120 mg/m2) with mannitol and prehydration was given every 4 weeks for two doses and then every 6 weeks. Of 24 patients evaluable for response, three had partial responses (3, 3+, and 9 months; response rate, 13%; 95% confidence limits, 4%-31%) and one had minor response. All responses occurred in previously untreated patients. High-dose DDP has modest activity in malignant mesothelioma.

Aged↗
PubMed1984

Phase-II trial of 1,2-diaminocyclohexane (4-carboxyphthalato) platinum (II) (DACCP) in non-small cell lung cancer.

A phase-II trial of the second-generation platinum analog 1,2-diaminocyclohexane (4-carboxyphthalato) platinum (II) (DACCP) was performed in 33 patients with non-small cell lung cancer. The compound was studied because of its lack of cross resistance in vitro and decreased nephrotoxicity in both preclinical testing and in a phase-I trial. The starting dose was 640 mg/m2 IV every 3 weeks, with escalations to 720 mg/m2 in the absence of toxicity. Myelosuppression and nephrotoxicity were uncommon. Allergic reactions and neurotoxicity were seen in five and three patients, respectively. Of 28 patients evaluable for response, one partial remission of 3 months' duration was noted in a patient who had previously responded but subsequently progressed during cisplatin and vindesine medication. No responses were seen in 11 adequately treated patients who had received no prior therapy. DACCP has only minimal activity in non-small cell lung cancer. No further studies are planned in this disease.

Adult↗
PubMed1983

Cisplatin, vindesine, and bleomycin chemotherapy of local-regional and advanced esophageal carcinoma.

Seventy-one patients with epidermoid carcinoma of the esophagus were treated with a three-drug combination of cisplatin, vindesine, and bleomycin. Forty-five patients had local-regional tumor and received chemotherapy prior to surgery or radiation therapy. Twenty-six patients with extensive disease were treated primarily with chemotherapy alone. The overall major objective response rate to cisplatin-vindesine-bleomycin was 53 percent (36 of 68 evaluable patients). Patients with local-regional disease had a higher response rate than those with extensive disease (63 and 33 percent, respectively). Following preoperative chemotherapy, 34 patients with local-regional disease underwent exploration. Resectable disease was present in 82 percent. There was no increase in operative morbidity or mortality (5.6 percent), when compared with historical control groups. The median survival for the preoperative chemotherapy group was 16.2 months, which is superior to that of a historical control group (p = 0.023). For patients with extensive disease, treated primarily with chemotherapy alone, the median duration of response was seven months. Toxicities of cisplatin-vindesine-bleomycin were in general well-tolerated, and included nausea and vomiting (seen less frequently because of extensive use of metoclopramide), alopecia, nephrotoxicity, and peripheral neuropathy. The dose-limiting toxicity was myelosuppression. Although conventional chemotherapeutic agents have little activity, these results indicate that the investigational combination of cisplatin, vindesine, and bleomycin can induce major regressions in a substantial proportion of patients with esophageal cancer. When this drug combination is used preoperatively, high resection rates and possibly improved survival are seen.

Adult↗
PubMed1983

Vindesine in the treatment of malignant mesothelioma: a phase II study.

Vindesine (VDS) is a new semisynthetic vinca alkaloid which has demonstrated therapeutic activity against a variety of solid tumors. A phase II trial of this agent was performed in patients with advanced malignant mesothelioma. VDS at a dose of 3 mg/m2 was given iv once weekly for 4-6 weeks and then every 2 weeks thereafter. Only one of 17 evaluable patients had a partial remission, lasting 5 months (95% confidence limits, 0%-17%). Toxic effects of VDS included leukopenia, peripheral neuropathy, and alopecia. VDS has minimal activity in malignant mesothelioma.

Adult↗
PubMed1982

Treatment of advanced esophageal cancer.

Over 90% of patients with epidermoid carcinoma of the esophagus will either present with or will develop advanced incurable disease within five years of diagnosis. The primary goal of therapy for these patients if palliation. A variety of surgical approaches have been used to restore or improve swallowing function. Gastrostomy tubes, dilation, or intraluminal tubes are the simplest procedures but do not usually allow use of a normal diet. More aggressive approaches involving bypass or palliative resection have a substantial morbidity and mortality but dietary intake is more normal. Radiation therapy, given in a palliative fashion, gives substantial relief from dysphagia in only 50% of patients, usually for a 2--6 month period. Although conventional chemotherapeutic agents are of little of no benefit, newer investigational drugs, used in combination, appear substantially more effective. The combination of cisplatin, vindesine, and bleomycin has been noted to induce major objective regressions in 50% of a group of 62 patients with either metastatic or locoregional disease. In patients with disease limited to the locoregional area, resection rates following preoperative therapy with cisplatin-based combination chemotherapy (with or without concommitant radiation) range from 75--85%. Whether the increased response rates seen with newer systemic agents will lead to improved disease-free and total survivals is not yet known.

Antineoplastic Agents↗
PubMed1982

Phase II trial of VP16-213 in non-small cell lung cancer (NSCLC).

Fifty-one patients with non-small cell lung cancer (NSCLC) were treated, during a phase II trial, with 4'demethylepipodophyllotoxin-beta-D-ethylidene glucoside (VP16-213). Forty-nine were evaluable for response, and of these two (4%) had partial responses lasting 5 and 6 months. Prior treatment with chemotherapy may have adversely affected response rate; none of the 24 previously treated patients had a major response. Myelosuppression was the dose limiting toxicity. Anorexia, nausea and vomiting, partial alopecia, and chills plus hypotension during drug infusion were the other toxic effects. We conclude that VP16-213 has only minimal activity as a single agent in NSCLC.

Adult↗
PubMed1982

Cisplatin, doxorubicin, cyclophosphamide, and vindesine combination chemotherapy for non-small cell lung cancer.

Seventy-four patients with non-small cell lung cancer were treated in a prospective, randomized trial either with a four-drug combination of cisplatin, doxorubicin, cyclophosphamide, and vindesine (PACE) or with a three-drug combination of cisplatin, cyclophosphamide, and vindesine (PCE). None of these patients had received prior chemotherapy, and all had a Karnofsky performance status of at least 60. Of 68 evaluable patients, 21 (31%) had complete or partial remissions. Response rates for PACE and PCE were similar, and there was no difference in response rates for patients with adenocarcinoma or epidermoid cancer. The median duration of remission was 10 months (range, 2-26+); five patients are still in remission (median, 18+ months; range, 17+ to 26+). The median duration of survival for responding patients (complete or partial) was 18 months. Toxic effects, including mild to moderate myelosuppression, peripheral neuropathy, and nephrotoxicity, were manageable in general. The response rates and remission durations for PACE and PCE are similar to those seen with the two-drug combination of cisplatin and vindesine, and toxic effects are similar. Thus, the addition of doxorubicin and/or cyclophosphamide adds no advantage to the use of the cisplatin and vindesine combination alone.

Adenocarcinoma↗
PubMed1982

Phase II study of methyl-GAG in the treatment of esophageal carcinoma.

Twenty-four patients with epidermoid carcinoma of the esophagus have been treated, in a phase II trial, with methyl-GAG using a weekly schedule. Eighteen patients had received prior chemotherapy with cisplatin-containing combinations. Of 23 evaluable patients, four (17%) had partial remissions, each lasting 2 months. All patients had received prior chemotherapy. Toxic effects were manageable and included mild nausea and vomiting, mucositis, and fatigue. Using this schedule, methyl-GAG had modest activity in esophageal cancer, with acceptable toxicity. Its role in combination chemotherapy remains to be defined.

Aged↗
PubMed1981

Phase II trial of methylglyoxal-bis-(guanylhydrazone) in non-small-cell lung cancer.

Fifty-two patients with metastatic or recurrent non-small-cell lung cancer (NSCLC) were treated, during a phase II trial, with methylglyoxal-bis-(guanylhydrazone) (MGBG). Of the 44 patients who had adequate trials, 4 had partial responses (PR), for an overall 9% PR rate. Response durations ranged from 3 to 5+ months. Prior treatment with chemotherapy may have adversely affected response rate; 15% of previously untreated patients responded, compared to only 4% of previously treated patients. A syndrome of weakness and fatigue was the most serious side effect. Anorexia and weight loss, stomatitis, nausea and vomiting, diarrhea, and peripheral neuropathy were the other toxic effects. We conclude that MGBG has activity in NSCLC, especially in previously untreated patients, and further studies are indicated in that population.

Adenocarcinoma↗
PubMedDate not supplied

Therapy of upper gastrointestinal tract cancers.

Esophageal and gastric cancers are highly virulent tumors with an especially poor prognosis. They are rather common tumors in the United States with an anticipated annual incidence of approximately 32,000 new patients in 1991. Adenocarcinomas of the proximal stomach and lower esophagus are rapidly increasing in incidence; the reasons for this remain unclear. Endoscopic ultrasonography has offered a new dimension to staging especially of the primary tumor but also shows promise for more accurate identification of nodal metastasis. While stage remains the single most important prognostic variable, biological studies investigating tumor markers are a high priority; aneuploidy and HER-2/neu amplification or overexpression may predict poor outcome in gastric cancer. Esophageal and gastric cancers have a high local and distant failure rate when treated with conventional therapy. New developments in chemotherapy in the neoadjuvant and postoperative setting are under intense investigation in an attempt to improve prognosis for these diseases.

Combined Modality Therapy↗
PubMedDate not supplied

Adjuvant postoperative radiation therapy for resectable rectal cancer.

Following potentially curative surgery for resectable adenocarcinoma of the rectum, the incidence of local failure is 15% to 35% in stages T3N0 and T1N1-2 and 45% to 65% in stages T4N0, T3N1-2, and T4N1-2. In order to determine the impact of pelvic radiation therapy +/- chemotherapy on local failure and survival, we present a prospective analysis of our results of 25 patients treated with this approach. The median follow-up was 30 months (range: 10 to 48 months). For the total patient group the 3-year actuarial survival was 74%. In order to more accurately analyze the patterns of failure, actuarial calculations were performed. The actuarial incidence of local failure as a component of failure was 17%. For patients with node positive disease (T1-4N1-2), the overall survival was 80%, and the actuarial incidence of local failure as a component of failure was 15%. Complications were acceptable and the incidence of small bowel obstruction requiring surgery was 8%.

Adenocarcinoma↗