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Biomedical subjects

D F Bajorin

Publications and source records attributed to D F Bajorin.

87 records · Page 5Linked to original sources
PubMed1991

Continuous infusion gallium nitrate for patients with advanced refractory urothelial tract tumors.

A Phase I-II trial of gallium nitrate was conducted in 40 patients with bidimensionally measurable urothelial tract tumors who had failed to respond to combination chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin. Partial responses were observed in 4 of 23 patients (17.4%) who received 350 mg/m2/d or more for 5 days by continuous intravenous infusion. In two additional patients who received 350 mg/m2/d or more, a minor response and a mixed response were observed. The median duration of response was 4 months (range, 2 to 8 months). A dose-response relationship was suggested because no responses were observed in 17 patients who received less than 350 mg/m2/d. Myelosuppression was minimal. The dose-limiting toxic reaction was a reversible optic neuropathy that occurred in 3 of 11 patients who received 400 mg/m2/d. Further evaluation of infusional gallium nitrate is warranted in patients with urothelial tract malignant tumors.

Adult↗
PubMed1991

A phase II trial of high-dose cisplatin and dacarbazine. Lack of efficacy of high-dose, cisplatin-based therapy for metastatic melanoma.

Cisplatin and dacarbazine are used widely in the treatment of metastatic melanoma. To evaluate high-dose cisplatin and dacarbazine, 32 patients with metastatic melanoma were treated with cisplatin 50 mg/m2 and dacarbazine 350 mg/m2 daily for three days repeated at 28-day intervals. Their median age was 43.5 years (range, 25 to 73 years), and their median Karnofsky performance status was 80% (range, 70% to 100%). Measurable and evaluable disease sites (number of patients) included lymph nodes (22), lung (17), soft tissue (16), liver (13), bone (seven), spleen (four), adrenal gland (three), skin (three), and other sites (five). Patients received a median of two cycles of therapy (range, one to eight cycles). Thirty patients were evaluable for response. No complete responses were observed. Five patients had a partial response (17%; 95% confidence interval, 3% to 30%) for 16+, 12+, 7, 6.5, and 3 months. Responding sites of disease included lymph nodes (five of 22), lung (three of 17), and soft tissue (two of 16). Hematologic toxicity (Grade greater than or equal to 3) included neutropenia (16 of 32 patients, 30 of 90 cycles), thrombocytopenia (eight of 32 patients, 12 of 90 cycles), and anemia (five patients). Nine episodes of neutropenia and fever were seen in four patients; two had bacteremia. Nonhematologic toxicity (Grade greater than or equal to 3) included hypotension (two patients), nausea and vomiting (four), neuropathy (two), ototoxicity (four), and hypomagnesemia (nine). The low objective response rate and severe toxicity of this regimen preclude its standard use in patients with metastatic melanoma. A review of cisplatin-based therapy in metastatic melanoma suggests that there is no dose-response relationship. The use of high-dose cisplatin (greater than 100 mg/m2) in the treatment of metastatic melanoma is not recommended.

Adult↗
PubMed1991

Genetic analysis as an aid in diagnosis for patients with midline carcinomas of uncertain histologies.

The tumors of nine patients with carcinomas of uncertain histogenesis (eight with poorly differentiated carcinomas involving primarily midline structures and one with a diagnosis of seminoma and atypical clinical features) were studied by cytogenetic and Southern blot analyses. Four of the eight patients with poorly differentiated carcinomas had abnormalities of chromosome 12 consistent with a diagnosis of germ cell tumor. These abnormalities comprised an i(12p) in two patients and a del(12q) in a third patient detected by cytogenetic analysis and multiple copies of 12p detected by Southern blot analysis in a fourth patient. Three of these four patients with a diagnosis of germ cell tumor established by genetic analysis achieved a complete response to cisplatin-based chemotherapy. The tumor biopsy of one patient showed a t(11;22) (q24;q12), and this patient had chemotherapy directed to neuroepithelioma. Cytogenetic analysis was unsuccessful for the tumors of three patients; these tumors did not have multiple copies of 12p detected by Southern blot analysis. These patients did not respond to cisplatin-based chemotherapy. One patient with a diagnosis of extragonadal seminoma failed to respond to cisplatin-based chemotherapy and had a second tumor biopsy performed that demonstrated a t(8;14) (q24;q32). This patient's diagnosis was changed to a non-Hodgkin's lymphoma. Thus, genetic analysis provided a diagnosis in six of nine patients. Cytogenetic and molecular analyses are useful clinical tools for the determination of histogenesis in some patients with poorly differentiated carcinomas of uncertain histology.

Adult↗
PubMed1991

Two-drug therapy in patients with metastatic germ cell tumors.

Eighty-two patients with metastatic germ cell tumors (GCT) treated with two-drug therapy consisting of etoposide and cisplatin were evaluated for late relapse. Good-risk GCT was defined using Memorial Sloan-Kettering Cancer Center (MSKCC) criteria. Etoposide was given at 100 mg/m2 on days 1 to 5 and cisplatin was given at 20 mg/m2 on days 1 to 5; therapy was recycled at 21 days with delays up to 7 days for a leukocyte count of less than 3000/microliters or a platelet count of less than 100,000/microliters. Drug doses were not attenuated for myelosuppression. Seventy-six of 82 evaluable patients achieved a complete response (CR). Seventy-two patients had a CR to chemotherapy alone. Forty-six (56%) patients had excision of residual abnormalities: 11 had teratoma in the resected specimen, 31 had necrotic debris or fibrosis, and 4 had a CR after chemotherapy plus complete excision of residual viable GCT. Six patients had an incomplete response to chemotherapy; one of these patients had unresectable mature teratoma and remains progression-free. The median etoposide dose (+/- standard deviation [SD]) was 500 mg/m2/course (+/- 35 mg/m2) and the median cisplatin dose (+/- SD) was 100 mg/m2/course (+/- 6 mg/m2). Nine patients experienced a relapse at 6 to 17.5 months; two patients with nonseminomatous GCT were salvaged by chemotherapy and one patient with seminoma was salvaged by chemotherapy and radiation therapy. The three patients who were salvaged by additional therapy are disease-free at 59 to 63 months. Seventy-one patients (87%) remain disease-free with a median follow-up time of 63 months (range, 33 to 92 months). No relapses have occurred beyond 17.5 months. Etoposide and cisplatin therapy at these doses and schedule results in durable CR without late relapse.

Adult↗
PubMed1991

Phase II trial of N-methylformamide in patients with metastatic melanoma.

Sixteen patients with metastatic melanoma were treated with N-methylformamide (NMF), a polar-planar compound with in vitro cytotoxic and differentiating properties. Sixteen patients were evaluable for toxicity and 14 for response. The initial four patients received an intravenous bolus of NMF 800 mg/m2 daily for 5 consecutive days every 28 days. Because of excessive gastrointestinal toxicity, the dose was reduced to 700 mg/m2/day for the subsequent 12 patients. Two patients had immediate adverse effects from NMF; one had a grand mal seizure and the other developed severe abdominal pain. Nausea, vomiting and abdominal pain were dose-limiting. Transient elevation of liver function tests occurred in all patients. Myelosuppression was not observed. There were no objective responses among 14 evaluable patients (95% confidence limits 0-20%). One patient with pulmonary metastases had a minor response lasting 13 months. Median time to progression of disease was one month. NMF in these doses and schedule lacks clinical efficacy in the treatment of metastatic melanoma.

Adult↗
PubMed1991

Phase II trial of cisplatin and etoposide in patients with metastatic melanoma.

Fourteen patients with metastatic melanoma were treated with cisplatin and etoposide by bolus intravenous infusion daily for 5 consecutive days each month. All patients were evaluable for toxicity and twelve for response. Eight patients were treated with cisplatin 20 mg/m2 and etoposide 100 mg/m2 daily. Because of excessive myelosuppression, the daily dose of etoposide was reduced to 75 mg/m2 in the remaining six patients. There were no major responses among 12 evaluable patients (major response rate less than or equal to 24% with 95% confidence). The median time to progression was one month. One patient with a liver metastasis had a minor response lasting 6+ months. The combination of cisplatin and etoposide in these doses and schedule lacked sufficient clinical efficacy in the treatment of metastatic melanoma.

Adult↗
PubMed1991

Assessment of risk in metastatic testis carcinoma: impact on treatment.

The majority of patients have 'good risk' nonseminomatous germ cell tumors, that is, they are likely to obtain an initial complete response to chemotherapy. Trials in these patients attempt to reduce the toxicity of chemotherapy. The minority of patients have refractory disease ('poor risk' nonseminomatous germ cell tumors) and the primary objective in this population is to improve the proportion of complete response. Chemotherapy trials for the poor risk group are generally associated with greater toxicity. Clinical factors reported to impact on the prognosis of nonseminomatous germ cell tumor patients include the pretreatment level of serum tumor markers (AFP, HCG, LDH), extern or bulk of disease, the pathology and the site of the primary lesion. No consensus currently exists on which factors are most important in determining prognosis and how they should be used to allocate patients to good and poor risk nonseminomatous germ cell tumors trials. The data support the concept that biologic markers and extent or bulk of disease together are more predictive of response and survival than either one alone and their combined use results in a smaller percent of the germ cell tumor population allocated to poor risk trials. This minimizes exposure of good risk patients to toxic regimens and still maintains a high response rate in the good risk population. The current eligibility criteria for good and poor risk trials in use directly affects the reported response proportion and survival. In view of these differences, good and poor risk trials should be randomized against a comparative control population and nonrandomized trials comparing treatment results with those of other studies or historical controls should be viewed with extreme caution.

Biomarkers, Tumor↗
PubMed1990

The role of ifosfamide plus cisplatin-based chemotherapy as salvage therapy for patients with refractory germ cell tumors.

A prospective study of four cycles of etoposide with ifosfamide and cisplatin (VIP) chemotherapy was conducted in 42 germ cell tumor (GCT) patients who were refractory to cisplatin with etoposide/vinblastine-based therapy. Forty patients were evaluable for response. Ten patients (25%) had a complete response: seven to chemotherapy alone and an additional three patients after surgical resection of viable GCT. With a median follow-up of 15 months, four complete responders relapsed, and six patients (15%) remain in remission. Hematologic and nephrotoxicity were moderately severe. Durable complete responses with VIP as second salvage were achieved and suggests that ifosfamide adds efficacy to standard first-salvage therapy. The observed nephrotoxicity and myelotoxicity are considerations in the design of ifosfamide-cisplatin-based regimens. Hematopoietic growth factors may be useful in ameliorating myelotoxicity. The early use of ifosfamide-based chemotherapy may reduce the nephrotoxicity exacerbated by prior cisplatin. A trial of VIP as first salvage after a relapse from a complete response to platinum-based induction therapy is warranted. The modest proportion of patients who achieve a durable remission to VIP as second salvage emphasizes the need for more efficacious salvage therapy for patients who do not achieve a durable complete response.

Adolescent↗
PubMed1990

Phase I evaluation of a combination of monoclonal antibody R24 and interleukin 2 in patients with metastatic melanoma.

A combination of recombinant human interleukin 2 (rhIL-2) and mouse monoclonal antibody R24 (recognizing the ganglioside GD3) was evaluated in patients with metastatic melanoma in a phase I trial. rhIL-2 was given at a constant daily dose of 1 x 10(6) units/m2 i.v. over 6 h on days 1-5 and 8-12. R24 was given on days 8-12 at four dose levels (1, 3, 8, and 12 mg/m2 daily). Twenty patients were evaluable for toxicity and response, five at each dose level. The toxicity of the combination was not overlapping and generally mild. There was a rebound peripheral blood T-lymphocytosis at the end of treatment increasing with the dose of R24. The median lymphocyte count on day 12 of treatment was 3108 +/- 554/ml in patients treated at R24 doses of 8 and 12 mg/m2 versus 2239 +/- 672/ml at doses of 1 and 3 mg/m2. This evidence and other data suggested that R24 enhanced IL-2-mediated T-cell activation in vivo. Two patients demonstrated increases in R24-mediated antibody-dependent cellular cytotoxicity for GD3-expressing cells during treatment. rhIL-2 appeared to accelerate the development of human anti-mouse antibody; three patients developed human anti-mouse antibody by the fifth day of R24 treatment, earlier than observed in prior studies using R24 alone and one patient during the first week of rhIL-2 alone, prior to R24 treatment. One patient had a partial response in soft tissue sites lasting 6 months and two patients had minor responses. This clinical trial extends the previous observation that R24 enhances lymphocyte proliferation in vitro.

Adult↗
PubMed1986

Pharmacokinetics of cis-diamminedichloroplatinum(II) after administration in hypertonic saline.

Nephrotoxicity, the dose-limiting toxicity of cis-diamminedichloroplatinum(II) (CDDP), is ameliorated when administered in hypertonic saline with normal saline hydration. To determine whether the diminished nephrotoxicity is associated with alteration of the pharmacokinetics of CDDP, we examined the pharmacokinetics of free and total platinum, platinum renal excretion, and urine electrolytes in patients given CDDP in hypertonic saline and in patients given CDDP in a conventional manner. The pharmacokinetics of free and total platinum for equal doses of CDDP were similar regardless of the vehicle of administration and the method of hydration. CDDP given in a vehicle of high chloride concentration with normal saline hydration resulted in a statistically significant increase in both urine volume and chloruresis compared to the conventional regimen. The decreased nephrotoxicity associated with administration of CDDP in hypertonic saline with saline diuresis may be related to increased chloruresis, urinary volume, or a combination of both, but did not appear to be related to an alteration in the pharmacokinetics.

Adult↗
PubMedDate not supplied

Immunotherapy with monoclonal antibodies in metastatic melanoma.

Therapy for metastatic melanoma has been disappointing to date. Treatment with chemotherapy only uncommonly results in complete responses and rarely results in long-term survivors. The identification of human melanoma cell surface antigens has led to the development of an array of mouse monoclonal antibodies (MAb) for use in the diagnosis and therapy of patients with metastatic melanoma. Strategies utilizing MAbs based on immunologic approaches have been developed. Naked MAbs directed against glycoprotein surface antigens or conjugated to toxins or radionuclides have shown little biologic or clinical activity. However, phase I studies of MAb directed against glycolipid antigens have yielded objective tumor shrinkage with occasional complete responses. Severe toxicity has been seen infrequently. Possible anti-tumor mechanisms include complement activation and antibody-dependent cellular cytotoxicity utilizing natural killer cells or monocytes as effector cells. Strategies to enhance the anti-tumor effects of MAb, including combinations with cytotoxic agents and cytokines, have been introduced with limited success thus far. The development of a human IgG anti-mouse antibody has been seen in nearly all treated patients. A new generation of MAb engineered to overcome the immunogenicity of mouse MAb and to enhance immune effector function will soon enter clinical trials.

Antibodies, Monoclonal↗