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Biomedical subjects

D Kelsen

Publications and source records attributed to D Kelsen.

At least 55 records · Page 3Linked to original sources
PubMed1990

Interferon alpha-2a and 5-fluorouracil for advanced colorectal carcinoma. Assessment of activity and toxicity.

Preclinical data showed that the cytotoxic effects of 5-fluorouracil (5-FU) are augmented by interferon (IFN). In a small study, 13 of 17 patients with advanced colorectal cancer responded to a regimen of 5-FU with IFN. Using the same dose and schedule as in this pilot study, 38 previously untreated patients with metastatic colorectal carcinoma were treated with continuous intravenous (IV) infusion of 5-FU 750 mg/m2 daily for 5 days, followed by weekly bolus 5-FU at 750 mg/m2 and subcutaneous IFN at 9 million units three times per week. Of 35 evaluable patients, nine (26%) had a partial response (95% confidence limit, 11% to 41%), with a median response duration of 7.5 months (range, 4.4 to greater than 11.7 months). Seven patients (20%) had a minor response, and ten (28%) had stable disease. The most common toxicities observed were stomatitis (52%) and diarrhea (43%). Neurotoxicity was seen in 34% of patients and consisted of gait disturbance, dizziness, confusion, memory loss, and dementia. Because of toxicity, 84% of patients required a reduction of the IFN dose by at least 50%, and 63% required reduction of the 5-FU dose by at least 25%. Although the combination of 5-FU and IFN in patients with advanced colorectal carcinoma has some activity, the regimen was toxic, and the observed response rate (26%) was not substantially superior to alternative 5-FU programs.

Adult↗
PubMed1990

A phase I trial of cisplatin in hypertonic saline and escalating doses of 5-fluorouracil by continuous intravenous infusion in patients with advanced malignancies.

Thirty-four patients with incurable solid tumors were treated in a Phase I trial with a fixed dose of high-dose cisplatin (CDDP) administered in hypertonic saline and escalating doses of infusional 5-fluorouracil (5-FU). Five treatment levels of 5-FU, ranging from 500 to 900 mg/m2/day for 5 days, were studied. Leukopenia, thrombocytopenia, and oral mucositis were the dose-limiting toxicities encountered. Nephrotoxicity was minimal. Ototoxicity and peripheral neuropathies were rare and mild in this patient group, but most patients received only a small number of treatment cycles. Diarrhea was not dose-limiting. Two complete responses (one non-small cell lung cancer and one sweat gland carcinoma) were observed. No other major responses were noted. With the dose of CDDP set at 35 mg/m2/day for 5 consecutive days, the maximum tolerated dose (MTD) of a concurrent 5-day 5-FU infusion was found to be 900 mg/m2/day. The recommended dosages for Phase II trials are 35 mg/m2/day CDDP and 800 mg/m2/day 5-FU for 5 consecutive days. Cancers of the lung, breast, gastrointestinal tract, and genitourinary tract would be reasonable targets for Phase II studies.

Adenocarcinoma↗
PubMed1990

A phase II trial of recombinant tumor necrosis factor in patients with advanced colorectal carcinoma.

Sixteen previously treated (with only one prior regimen) patients with histologically proven metastatic or locally recurrent colorectal carcinoma were treated with recombinant tumor necrosis factor (rTNF) administered by 30-minute i.v. infusions twice daily for 5 consecutive days every other week for 8 weeks. Patients received 100 micrograms/m2 twice daily on day 1 of cycle 1 with escalation to 150 micrograms/m2 twice daily thereafter. Patients were concomitantly treated with indomethacin 25 mg every 6 hours and acetaminophen 650 mg every 4 hours to obviate fever and chills. Toxicities included: nausea/vomiting (69%), headache (25%), chills (69%), pain at tumor sites (63%), hypotension (31%), and hypertension (38%). Hematologic toxicity included leukopenia less than 2000 cells/mm3 (38%) and thrombocytopenia less than 100,000 cells/mm3 (13%). Liver function abnormalities occurred independently of the site or extent of metastatic disease and inconsistently in each treatment cycle. Four patients developed bilirubinemia greater than 2.5 x baseline values (range, 2.5 to 10.3 U/L); five patients had greater than 2.5 x elevations in alkaline phosphatase (range, 624 to 1663 U/L). Two patients developed retinal vein thrombosis in the absence of hemostatic abnormalities. In both instances, this complication occurred several weeks after completion of therapy. No objective responses were noted in 14 evaluable patients (95% confidence interval: 0 to 0.23). Three patients had stable disease for a median duration of 4.5 months. In conclusion, i.v. rTNF at this dose and schedule has no demonstrable antitumor efficacy. Twice-daily i.v. administration of this agent is associated with more hepatotoxicity than previously reported in trials using subcutaneous or once daily i.v. administration. Retinal vein thrombosis may be a late complication of i.v. rTNF at this dose and schedule.

Aged↗
PubMed1990

Phase II trial of carboplatin and vinblastine in adenocarcinoma of the stomach.

Twenty-five previously untreated patients with advanced adenocarcinoma of the upper gastrointestinal tract were treated with a combination of carboplatin and vinblastine. Two partial responses (duration three months and six months) were seen among 22 evaluable patients. Myelosuppression was the most common toxicity and was generally mild. The 8% response rate, (95% confidence interval 2 to 24%) observed in this study indicated that carboplatin-vinblastine has only modest activity in adenocarcinoma of the upper gastrointestinal tract. Although less toxic, this regimen appears to be less effective than previously reported cisplatin-containing regimens in adenocarcinoma of the upper GI tract.

Adenocarcinoma↗
PubMed1990

Phase II study of CHIP chemotherapy in advanced adenocarcinomas of the upper gastrointestinal tract.

Iproplatin (CHIP) is a second generation cisplatin analogue which has completed its Phase I trials. We studied the efficacy and toxicity of CHIP in 36 previously untreated patients with advanced upper gastrointestinal tract adenocarcinomas (GE junction, cardia, antrum and body of the stomach). The starting dose was 275 mg/m2; course were repeated on an every four week schedule. Thirty-five patients were evaluable for response. Three partial remissions (8.5%) [95% confidence limits 2.5-15%] were seen. Toxicity was tolerable and included mild myelosuppression and mild nausea and vomiting. Although well tolerated, in patients with gastric and GE junction adenocarcinomas, CHIP chemotherapy was not more and probably slightly less, effective than the parent analogue cisplatin.

Adenocarcinoma↗
PubMed1989

Advanced pancreatic cancer: a phase I-II trial of cisplatin, high-dose cytarabine, and caffeine.

In a phase I-II study, 28 patients with advanced pancreatic adenocarcinoma were treated with cisplatin, high-dose cytarabine (ARA-C), and caffeine. This clinical trial was based on a nude mouse-human tumor xenograft model, which demonstrated synergism of these agents by inhibiting the growth of human pancreatic tumors. Toxic effects noted in the clinical study included myelosuppression, moderate nausea and vomiting, and mild renal insufficiency. No toxic effects were directly attributable to caffeine. Eighteen of the 28 patients had measurable or assessable disease; seven (39%) had partial responses (95% confidence intervals, 18%-63%). The median response duration was 6.2 months. Median survival for responders was 9.5 months with two patients surviving for more than 18 months. Median survival for all patients was 6.1 months. The combination of cisplatin, ARA-C, and caffeine is an active and tolerable regimen in the treatment of advanced pancreatic cancer. A phase III trial in which this regimen is being compared with standard therapy is in progress.

Acute Disease↗
PubMed1989

Neoadjuvant therapy of esophageal cancer.

Neoadjuvant (preoperative) chemotherapy, with or without radiotherapy, is under intense study. There are theoretical and practical reasons for the preoperative use of systemic therapy: (a) laboratory studies support the use of preoperative treatment in animal models, (b) the relapse pattern of esophageal cancer is primarily systemic and (c) the impact on palliation if response is associated with an improved resection rate. Three techniques involving systemic therapy are currently under investigation: (a) chemotherapy alone followed by a planned surgical procedure; (b) chemotherapy and concurrent radiotherapy followed by a planned surgical procedure; (c) chemotherapy and radiotherapy without surgery. Phase II trials of the first technique have demonstrated its feasibility without an increase in operative morbidity or mortality. Two small-scale phase III trials have confirmed chemotherapy's efficacy but have not clearly demonstrated an impact on survival. Large-scale phase III trials are under way, or about to begin, to test definitively the hypothesis that neoadjuvant chemotherapy improves disease-free and overall survival in operable patients. The second technique has also been tested in small-scale phase II trials. Most recently, a large-scale phase II trial has been reported which suggests that this technique has not had a major effect on resection rates or on long-term survival for most patients. These treatment plans are tolerable if careful attention to detail is given. Definitive phase III trials testing the superiority of multimodality treatments over radiotherapy alone or surgery alone are under way.

Adjuvants, Pharmaceutic↗
PubMed1988

Randomized trial of combined modality therapy with and without thymosin fraction V in the treatment of small cell lung cancer.

A randomized trial of thymosin fraction V (60 mg/m2 s.c. twice weekly) given during induction chemotherapy and radiation therapy was performed in 91 patients with small cell carcinoma of the lung. Induction chemotherapy consisted of four cycles of an alternating combination of drugs (cyclophosphamide/Adriamycin/vincristine and cisplatin/etoposide). Radiation to the primary complex was given to patients with limited disease. All patients received prophylactic cranial irradiation. There were 35 patients with limited disease (18 randomized to thymosin and 17 to no thymosin) and 56 with extensive disease (28 thymosin and 28 no thymosin). Pretreatment immunological parameters were comparable between the two groups. For limited disease patients the overall response rate was 100%, including 66% (21 of 32) complete responders. The median duration of response was 19 mo (range, 5-57 mo) and survival 21 mo (range, 4 days to 57 mo). The 3-yr survival was 32%. For ED patients the overall response rate was 95% with 29% (13 of 48) complete. The median duration of response was 10 mo and the median duration of survival 12 mo with 13% alive at 2 yr. A comparison of the thymosin-versus no thymosin-treated patients revealed no difference in response rate, response duration, or survival whether analyzed as a whole or by extent of disease. An analysis based on pretreatment immune function and total white blood cell and absolute lymphocyte count revealed no difference in the survival distributions. No differences in the pattern of toxicity were observed between the thymosin- versus no thymosin-treated patients. The addition of thymosin fraction V during induction chemotherapy and consolidation radiotherapy did not alter outcome.

Carcinoma, Small Cell↗
PubMed1988

A phase II trial of streptozotocin and adriamycin in advanced APUD tumors.

Thirty-three patients with advanced carcinoid tumors, islet cell carcinomas, or medullary carcinomas of the thyroid were entered into a phase II trial combining streptozotocin (STZ) and Adriamycin. Thirty-one patients are evaluable for response, and 29 are evaluable for survival. Six (19%) patients achieved objective partial responses (95% confidence limits: 5.4-33). The median duration of response for partial responders was 282 days. The median survival for responders and nonresponders was 16.2 months and 7.8 months, respectively, with an overall median survival of 10.9 months. At 10.9 months median follow-up, 4 (14%) of 29 patients are surviving. Toxicity was mild, except that nausea or vomiting occurred in 25 of 31 patients evaluable for toxicity. With this dose and schedule of administration, STZ and Adriamycin produce modest response rates with objective palliation of disease in patients with advanced amine precursor uptake and decarboxylation (APUD) tumors.

Adenoma, Islet Cell↗
PubMed1988

Phase II trial of mitoxantrone in advanced gastric cancer.

A Phase II trial of mitoxantrone was performed in patients with advanced adenocarcinoma of the stomach. All patients had measurable or evaluable disease, and none had received prior chemotherapy. Mitoxantrone was administered intravenously at a dose of 14 mg/m2 every 3 weeks. The major toxicity seen was myelosuppression. The drug was, in general, well tolerated. No major objective responses were seen. We conclude that mitoxantrone has less than 20% activity in this patient population. No further studies are planned.

Adult↗
PubMed1988

Phase I trial of concurrent intraperitoneal and continuous intravenous infusion of fluorouracil in patients with refractory cancer.

In an effort to maximize both local-regional and systemic drug exposure to tumor in the peritoneal cavity, a phase I study was conducted that examined the simultaneous daily intraperitoneal (IP) and continuous intravenous infusion (CVI) of fluorouracil (5-FU) to 32 patients with refractory cancer. IP 5-FU administered at 1,000 mg/d with concurrent 5-FU by CVI at 1,000 mg/m2/d for four consecutive days was well tolerated. One patient with a primary gastrointestinal (GI) malignancy with minimal volume disease experienced a surgically defined complete remission. In theory, this regimen may demonstrate clinical utility as an adjuvant treatment of certain GI malignancies. Future studies are planned in this clinical setting.

Drug Administration Schedule↗
PubMed1987

Radiation-induced angiosarcoma.

A 47-year-old woman presented with an angiosarcoma of the terminal ileum 14 years after receiving adjuvant radiation therapy for ovarian dysgerminoma. Her clinical course is described, and the previously reported cases of radiation-induced angiosarcoma are reviewed.

Combined Modality Therapy↗
PubMed1987

Phase II trial of etoposide in APUD tumors.

Thirty-three patients with advanced, metastatic APUD tumors (islet cell, carcinoid, or medullary carcinomas of the thyroid) were treated with etoposide as a single agent. Of 29 evaluable patients, four (14%) had partial responses (95% confidence limits, 1%-26%). Toxic effects seen were those previously reported for etoposide as a single agent. Etoposide has activity in APUD tumors; further studies with this agent are indicated.

Adenoma, Islet Cell↗