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Biomedical subjects

M G Kris

Publications and source records attributed to M G Kris.

143 records · Page 8Linked to original sources
PubMed1985

Phase 1 trial of levonantradol in chemotherapy-induced emesis.

Levonantradol is a synthetic cannabinoid with demonstrated preclinical antiemetic activity. The current phase I trial was undertaken to determine: 1) the maximally tolerated dose; 2) the side effects at the different dosage levels; and 3) to evaluate the antiemetic efficacy of levonantradol in patients receiving emesis-producing chemotherapy. Thirty-four patients received 52 courses of levonantradol. Concurrent chemotherapy most frequently consisted of high dose cisplatin (120 mg/m2), either alone or in combination with other agents. Levonantradol dosage was escalated through seven treatment levels (0.5-4.0 mg per dose) and was given intramuscularly every 4 hours. Toxicity was similar to that observed with other cannabinoids and primarily consisted of dizziness (65%), burning and erythema at the injection site (48%), mild sedation (44%), orthostatic hypotension (37%), dysphoria (29%), and urinary retention (10%). Marked urinary retention occurred in three of seven patients at the 4.0 mg per dose level, and two of 24 patients at either the 2.5 mg and 3.0 mg levels. Major or minor antiemetic responses (0-2 or 3-5 emetic episodes, respectively) occurred in 23% of patients receiving cisplatin and in 53% of patients receiving non-cisplatin containing chemotherapy. Intramuscular levonantradol can be given safely at doses up to 3.0 mg/kg, with toxicity and antiemetic efficacy similar to that observed with other cannabinoids.

Adult↗
PubMed1985

Incidence, course, and severity of delayed nausea and vomiting following the administration of high-dose cisplatin.

Although many trials have evaluated the severity and treatment of nausea and vomiting immediately after cisplatin administration, no studies have focused on vomiting occurring more than 24 hours after chemotherapy--delayed emesis. Two consecutive trials were undertaken to evaluate the incidence, course (trial 1), and severity (trial 2) of delayed nausea and emesis and to develop methods to study these conditions. Eighty-six patients receiving cisplatin (120 mg/m2) for the first time were entered. On the day of cisplatin treatment, all received intravenous (IV) metoclopramide (3 mg/kg X 2 doses) plus dexamethasone (20 mg IV X 1 dose) with either diphenhydramine (50 mg IV) or lorazepam (1.0 to 1.5 mg/m2). Sixty-two percent of patients experienced no vomiting during the 24 hours immediately after administration of cisplatin. Overall, 93% of studied patients experienced some degree of delayed nausea or vomiting from 24 to 120 hours after cisplatin. In trial 1, the incidence of delayed vomiting ranged from 21% to 61% and delayed nausea from 24% to 78% in 58 patients. The highest incidence of both delayed nausea and emesis occurred during the period from 48 to 72 hours after administration of cisplatin. Patients who had no emesis during the initial 24 hours after cisplatin were less likely to experience delayed emesis. The severity of delayed nausea and vomiting was evaluated in 28 patients in trial 2. The amount of delayed nausea and vomiting was assessed daily by patients using a visual analogue scale and by an observer rating. The highest nausea and vomiting scores were seen during the period from 48 to 72 hours after administration of cisplatin, with acceptable correlation between patient scores and observer ratings. Although the nausea and vomiting occurring 24 or more hours after cisplatin administration is not as severe as that seen during the initial 24 hours after administration of cisplatin in patients not receiving antiemetics, it is a common condition that merits both further study and specific treatment.

Adult↗
PubMed1985

Trial of vindesine plus mitomycin in stage-3 non-small cell lung cancer. An active regimen for outpatient treatment.

Ninety patients with stage-3 non-small cell lung cancer were given vindesine (3 mg/sq m) plus mitomycin (10 mg/sq m). Data on response are available for 84 adequately treated individuals (93 percent). For patients who had received no prior chemotherapy, the rate of major objective response was 36 percent (20/55). For previously treated patients the rate of major response was 17 percent (5/29). The drugs were routinely administered in the outpatient department without difficulty. Moderate or severe myelosuppression, neurotoxic, nephrotoxic, or pulmonary toxic effects, nausea, and vomiting occurred in less than 15 percent of all studied patients. Three-drug extravasation ulcerations occurred in 1,129 administrations of chemotherapy (0.3 percent). There were two treatment-related deaths, one from sepsis and one from the combination of mitomycin-induced pulmonary and renal toxic effects. The combination of vindesine plus mitomycin is an active, well-tolerated outpatient regimen for patients with non-small cell lung cancer who have not previously received chemotherapy. Further trials are warranted to compare this regimen to other active combinations and to use it as a component of a program of treatment using alternating regimens of chemotherapy.

Adenocarcinoma↗
PubMed1985

Randomized trial comparing vindesine plus cisplatin with vinblastine plus cisplatin in patients with non-small cell lung cancer, with an analysis of methods of response assessment.

One hundred eight patients with stage III non-small cell lung cancer were randomly assigned to receive cisplatin (120 mg/m2) with either vindesine (3 mg/m2) or vinblastine (6 mg/m2). None had previously received chemotherapy. An additional goal was to determine if the observation of visible evaluable lesions was as accurate a method of response assessment as the observation of bidimensionally measurable lesions in non-small cell lung cancer. When vindesine plus cisplatin was compared to vinblastine plus cisplatin, response rates (33% vs 41%), median response durations (8.6 vs 5.6 months), and median survival times of responding patients (18.4 vs 16.2 months) were similar. Response rates, response durations, and survival times of responding patients determined through the observation of evaluable or measurable indicator lesions did not differ significantly. More patients receiving vinblastine plus cisplatin experienced wbc counts less than 2100/mm3 (P = 0.003). The two regimens demonstrated comparable response and survival data but clinically significant leukopenia was more common in vinblastine-treated patients. There was no difference in response data obtained through the study of patients with measurable and evaluable indicator lesions.

Adenocarcinoma↗
PubMed1985

Consecutive dose-finding trials adding lorazepam to the combination of metoclopramide plus dexamethasone: improved subjective effectiveness over the combination of diphenhydramine plus metoclopramide plus dexamethasone.

Four consecutive trials were undertaken to study lorazepam at each of three dosage levels and diphenhydramine when used in combination with iv metoclopramide and dexamethasone in patients receiving cisplatin at 120 mg/m2. The combination containing diphenhydramine had been the most effective treatment identified in prior trials. Earlier studies have found lorazepam to be a useful adjunct to other antiemetic agents. Sixty-five patients who had never received chemotherapy or antiemetics were directly observed in the hospital for 24 hours following cisplatin. Overall, 56% of the patients experienced no emesis and 78.5% of the patients had two or fewer vomiting episodes during the study period. No significant differences were noted in the number of patients who experienced no emesis or two or fewer episodes among the four trials. More sedation was seen with the lorazepam-containing regimens; other side effects were similar in type and severity. The trial using the highest dose of lorazepam (1.5 mg/m2) demonstrated significantly greater patient satisfaction (P = 0.039) and less anxiety during therapy (P = 0.02) when compared with the diphenhydramine combination. We conclude that combinations of iv metoclopramide plus dexamethasone with either diphenhydramine or lorazepam are well tolerated and effective in controlling cisplatin-induced emesis. The regimens containing lorazepam produced better subjective evaluations, and the combination using the highest lorazepam dose tested showed superior patient satisfaction and less anxiety during therapy.

Adult↗
PubMed1983

Phase I trial of PCNU.

In a phase I trial, 28 patients with advanced solid tumors were given PCNU daily for 5 days by iv infusion over 20 minutes at 6-week intervals. The total dose for each course ranged from 25 to 150 mg/m2 in six escalation steps. Myelosuppression was dose-limiting, with a platelet count depression regularly observed at doses of greater than or equal to 82.5 mg/m2. Leukopenia occurred only at higher doses. Nausea was uncommon, and vomiting did not occur. There were no adverse drug-related effects on renal or hepatic function. No antitumor activity was observed. A dose range of 100-125 mg/m2 iv for each 5-day course (20-25 mg/m2/day) is recommended for phase II studies.

Adenocarcinoma↗
PubMedDate not supplied

Final report of the 70.2-Gy and 75.6-Gy dose levels of a phase I dose escalation study using three-dimensional conformal radiotherapy in the treatment of inoperable non-small cell lung cancer.

PURPOSE AND OBJECTIVE: Three-dimensional conformal radiotherapy (3D-CRT) is a mode of high-precision radiotherapy designed to increase the tumor dose and decrease the dose to normal tissues. This study reports the final results of the first two dose levels (70.2 Gy and 75.6 Gy) of a phase I dose-escalation study using 3D-CRT for the treatment of non-small cell lung cancer. PATIENTS AND METHODS: Fifty-two patients were treated with 3D-CRT without chemotherapy. The median age was 67 years (range, 39-82 years). The majority of patients had locally advanced cancer. Tumor was staged as I/II in 10%, IIIA in 40%, and IIIB in 50%. Radiation was delivered in daily fractions of 1.8 Gy, 5 days a week. A radiation dose level was considered complete when 10 patients received the intended dose without unacceptable acute morbidity. Toxicity was scored according to the Radiation Therapy Oncology Group grading scheme. RESULTS: Twenty patients were initially assigned to the 70.2-Gy level; 14 of them received the intended dose. Three patients experienced severe acute toxicity, two with grade 3 (requiring steroids or oxygen) and a third with grade 5 (fatal) acute radiation pneumonitis. Because of the grade 5 pulmonary toxicity, the protocol was modified, and only patients with a calculated risk of normal tissue complication of less than 25% were eligible for dose escalation. Patients who had a normal tissue complication probability (NTCP) of greater than 25% received a lower dose of radiation. An additional 18 patients were entered on the modified study; 11 of them received 70.2 Gy. One patient experienced grade 3 acute pneumonitis. Despite dose reduction in four patients because of an unacceptably high NTCP, two additional patients developed grade 3 pulmonary toxicity. Fourteen patients were accrued to the 75.6-Gy dose level, and 10 received the intended dose. One of the 10 patients experienced grade 3 pulmonary toxicity and one developed grade 3 esophageal toxicity. Three patients were treated to lower doses as a result of their calculated NTCP without toxicity, and one patient refused treatment. The 2-year local control, disease-free survival, and overall survival rates were 37%, 12%, and 24%, respectively. The median survival time was 11 months. DISCUSSION: Treatment to 70.2 Gy and 75.6 Gy using 3D-CRT was delivered with acceptable morbidity when NTCP constraints were observed. Local control was encouraging in these patients with locally advanced disease. Patients are currently being accrued to the 81-Gy level of the study.

Adult↗
PubMedDate not supplied

Dyspnea following vinblastine or vindesine administration in patients receiving mitomycin plus vinca alkaloid combination therapy.

Pulmonary toxicity is not commonly associated with the vinca alkaloids vinblastine and vindesine. Three patients receiving the combination of mitomycin plus vindesine or vinblastine developed acute dyspnea 1-5 hours following vinca alkaloid administration. Two of the three patients continued to receive therapy and both experienced symptoms with each subsequent vinblastine or vindesine injection. No other cause for the dyspnea could be detected. We conclude that, as in the three previously reported cases, shortness of breath can occur after the injection of vinblastine or vindesine in patients receiving mitomycin plus vinca alkaloid combination therapy.

Antineoplastic Combined Chemotherapy Protocols↗