Search PubMed⌕ Search

Biomedical subjects

R S Benjamin

Publications and source records attributed to R S Benjamin.

At least 73 records · Page 4Linked to original sources
PubMed1994

Pilot study of preoperative chemotherapy with cisplatin, vinblastine, and dacarbazine in patients with local-regional recurrence of melanoma.

BACKGROUND: Because the prognosis of patients with local-regional recurrence of melanoma treated with surgery alone usually is poor, the authors conducted a study designed to determine the efficacy of preoperative chemotherapy using cisplatin, vinblastine, and dacarbazine (CVD) in this patient population. METHODS: Eligibility included biopsy-proven, measurable, and potentially resectable local-regional disease in the form of lymph node metastases, satellite/in-transit metastases and/or local recurrence. CVD consisted of cisplatin, 20 mg/m2 intravenously (IV) on days 2-5; vinblastine, 1.6 mg/m2 IV on days 1-5; and dacarbazine, 800 mg/m2 IV on day 1 only, repeated every 3 weeks. Patients usually received two to three courses of CVD and then underwent surgery. Postoperatively, patients who responded continued CVD for a maximum of 8 courses; nonresponders received no further therapy. RESULTS: Of 52 consecutive patients (40 with lymph node involvement and 12 with skin metastases), 5 (10%) achieved a pathologic complete response and 20 (38%) achieved a partial response, for an overall response rate of 48% (95% confidence interval, 34-62). Of the five patients who achieved a pathologic complete response, three had attained a clinical complete response and one a partial response, and one had stable disease after initial chemotherapy. At a median follow-up of 54 months (range, 32-69 months), 38% of the patients remained disease free. CONCLUSION: Preoperative chemotherapy with CVD has significant activity in local-regional recurrences of melanoma, resulting in pathologic complete response in 10% of the patients. Because its impact on survival remains unclear, this treatment strategy should currently remain investigational. Preoperative chemotherapy, however, could be offered to certain patients with bulky, borderline resectable, regional disease for whom cytoreduction may make surgery easier or less mutilating.

Adult↗
PubMed1994

Myxoid liposarcoma. Experience with chemotherapy.

BACKGROUND: Myxoid liposarcoma (ML) is the most common type of liposarcoma. It has been classified as an intermediate grade tumor with a definite metastatic potential but a relatively indolent natural history. Little is known about its sensitivity to chemotherapy. METHOD: The authors reviewed their experience with chemotherapy in ML from 1986 to 1992. The patient population was identified through a search of the database maintained by the Department of Melanoma-Sarcoma Medical Oncology of the M.D. Anderson Cancer Center. RESULTS: Forty-four patients each with a histologically confirmed diagnosis of ML were identified. Twenty-one were treated with chemotherapy. The median age was 45 years (31-69 years); there were 14 men and 7 women. The ML in 19 patients was in the lower extremity, one in the head and neck, and one pelvic. The median size of the primary tumor was 15 cm (range, 7-48 cm) in maximum dimension. Of the 18 patients who received doxorubicin- and dacarbazine-based chemotherapy as a frontline regimen [median of 3 (2-9) cycles] and were evaluable for response, 8 (1 completed response, 7 partial responses) achieved an objective response (44%, 95% confidence interval 21-67%). Two of the remaining three patients who were also treated with a similar regimen were not evaluable for response (one received chemotherapy postoperatively, and the other received concomitant radiation and doxorubicin), and the third patient received ifosfamide as frontline chemotherapy because of a significant cardiac history. Seven patients received chemotherapy in the neoadjuvant setting, 13 for recurrent or metastatic disease, and 1 postoperatively after complete tumor resection. At the last follow-up, 10 patients were alive with no evidence of disease, 3 were alive with disease, and 8 had died. The median follow-up was 51 months (range, 6-199 months) from diagnosis. CONCLUSION: The authors conclude that doxorubicin- and dacarbazine-based chemotherapy is effective in the treatment of ML.

Adult↗
PubMed1994

A phase I trial of weekly lomustine in patients with advanced cancer.

BACKGROUND: Lomustine is a commercially available chloroethyl nitrosourea compound whose antitumor activity in vitro and in animal tumor models exceeds its activity in humans. Part of the poor clinical performance of this drug may be explained by dose-limiting subjective toxicity observed with the standard schedule of one oral dose of approximately 130 mg/m2 every 6-8 weeks. METHODS: Twenty patients were enrolled in a Phase I clinical trial of weekly oral lomustine. The first dose level was 24 mg/m2, with subsequent dose increases in increments of 6 mg/m2. Intrapatient dose escalations were allowed if there were no toxic reactions noted after 12 weekly doses. RESULTS: The dose-limiting toxic effect was the development of thrombocytopenia in 35% of patients (6 of 17) treated at 30 mg/m2 after a median of 12 weekly doses (range, 5-20 weeks), whereas in 18% of patients (3 of 17), neutropenia developed after a median of 12 weeks (range, 9-22 weeks). Grade 3 or Grade 4 hematologic toxicity developed in three of three patients whose doses were escalated to 36 mg/m2/week after showing no evidence of toxicity for 12-16 weeks at 30 mg/m2/week. Partial remission was observed in two patients with malignant melanoma, and stable disease was observed in two patients with hypernephroma. Nausea, vomiting, and malaise were not significant complications of treatment. CONCLUSION: Lomustine can be administered at a dose of 30 mg/m2/week for 12+ weeks to patients with cancer who have received previous treatment with minimal toxicity while retaining antitumor activity.

Administration, Oral↗
PubMed1994

Phase I trial of murine monoclonal antibody 14G2a administered by prolonged intravenous infusion in patients with neuroectodermal tumors.

PURPOSE: The purpose of this phase I trial was to determine the toxicity and maximum-tolerated dose (MTD) of murine monoclonal antibody (Mab) 14G2a (anti-GD2) in cancer patients. PATIENTS AND METHODS: Following tracer doses of iodine-131-labeled 14G2a to determine tumor uptake, 18 patients with refractory melanoma, neuroblastoma, or osteosarcoma received unlabeled 14G2a at total concentrations of 50, 100, and 200 mg/m2 administered as daily 24-hour infusions for 5 days. RESULTS: The overall sensitivity of external immunoscintigraphy was 64 of 74 known metastases (86%). Toxicity from prolonged infusion of 14G2a consisted of severe generalized pain, hyponatremia, fever, rash, paresthesias, weakness, and chronic refractory postural hypotension (two patients). Toxicity was less severe in pediatric patients. The MTD of Mab was 100 mg/m2. Sixteen of 18 patients developed human antimouse antibodies (HAMA) to 14G2a. Terminal-phase half-life (T1/2) of unlabeled Mab was 6.6 +/- 1.8 hours for patients receiving 50 mg/m2 and 39.5 +/- 13.3 hours at the 100-mg/m2 level. Tumor biopsies from six melanoma patients were positive for GD2 antigen, but only two of six had trace amounts of 14G2a present. Three mixed responses (two melanoma, one osteosarcoma) and two partial responses (PRs; neuroblastoma) were observed. CONCLUSION: Mab 14G2a has modest antitumor activity at the expense of significant toxicity. Dose-limiting neurologic sequelae may significantly limit phase II studies other than in pediatric patients with neuroblastoma.

Adolescent↗
PubMed1994

Kinetic response of human marrow myeloid progenitor cells to in vivo treatment of patients with granulocyte colony-stimulating factor is different from the response to treatment with granulocyte-macrophage colony-stimulating factor.

We previously demonstrated that granulocyte-macrophage colony-stimulating factor (GM-CSF) induced sustained increases in cycling of myeloid progenitors in patients with sarcoma. However, decreased proliferation of these cells to a slow- or noncycling state, below pretreatment levels, occurred within 1 to 2 days and maintained for at least 1 week after discontinuation of GM-CSF. To assess possible biological differences in GM-CSF and granulocyte (G)-CSF in such kinetic effects, we evaluated cycling status of marrow progenitors before, during, and after administration of recombinant human G-CSF (5 micrograms/kg/d subcutaneously [s.c.]) to six patients with sarcoma for 8 days. On the last (8th) day of G-CSF treatment, cycling rates of colony-forming units-granulocyte/macrophage (CFU-GM), burst-forming units-erythroid (BFU-E), and multipotent colony-forming units (CFU-GEMM) were enhanced 1.5- to 1.9-fold, to values of 40 +/- 10% to 58 +/- 5%. In sharp contrast to patients receiving GM-CSF, however, progenitor cells from patients off G-CSF treatment for 2 to 4 days were still rapidly proliferating. These differences in proliferative kinetics may be of use for design of clinical trials to efficaciously utilize these growth factors.

Bone Marrow↗
PubMed1994

Sarcoma of the breast: implications for extent of therapy. The M. D. Anderson experience.

BACKGROUND: Sarcoma of the breast is a rare clinical entity for which there are no prospective data about extent of surgery indicated or role of multimodality therapy. The purpose of this study was to examine one of the largest single institutional experiences to shed light on these clinical issues. METHODS: This study retrospectively reviewed 60 cases of sarcoma of the breast (cystosarcoma phyllodes excluded). RESULTS: For the entire series there was a median overall survival time (OS) of 67 months and a disease-free survival period (DFS) of 18 months. Tumors smaller than 5 cm were associated with a better DFS (p < 0.04) and OS (p < 0.009). Patients with tumors less than 5 cm in diameter did equally well whether treated by wide local excision or mastectomy. Angiosarcoma histologic characteristics were associated with longer OS than stromal sarcoma (p = 0.017), malignant fibrous histiocytoma (p = 0.075), or fibrosarcoma (p = 0.08). Axillary dissections did not recover any nodal metastasis; moreover, treatment in 75% of the patients with negative nodes subsequently failed. Regional lymph node metastases were always and only in the context of disseminated disease. Adjuvant chemotherapy and/or radiotherapy was associated with prolonged DFS (p = 0.015). There was a trend toward improved local control with adjuvant radiotherapy (p = 0.14). CONCLUSIONS: Lesions less than 5 cm should be treated by breast-preserving wide local excision, and adjuvant radiotherapy should be considered for selected subgroups. For tumors 5 cm or larger, a more aggressive approach seems appropriate; consideration should be given to neoadjuvant chemoradiation followed by margin-negative surgery (if possible). There is no demonstrable staging or therapeutic role for routine axillary dissection.

Adolescent↗
PubMed1993

Combination chemotherapy in adult desmoid tumors.

BACKGROUND: Desmoid tumors are locally aggressive tumors, with no metastatic potential, that generally are amenable to local treatments, such as surgery and radiation therapy. Systemic therapy is considered for selected cases that are not amenable to local treatment. METHODS: The authors reviewed their experience with chemotherapy in desmoid tumors. A patient population was identified through a search of the data base maintained by the Department of Patient Studies. RESULTS: Between January 1971 and December 1991, 180 patients with a histologically confirmed diagnosis of desmoid tumor were seen at the authors' institution. Twelve patients (8 male and 4 female patients; age range, 16-66 years; median age, 29 years) received chemotherapy. Eleven patients received doxorubicin (60-90 mg/m2) plus dacarbazine (750-1000 mg/m2)-based regimens for a median of 5 cycles (2-10 cycles). Six of the nine patients who could be evaluated for response had an objective response (two complete responses and four partial responses), one patient had a minor response, and two patients had stable disease. Two other patients treated in the early 1970s could not be evaluated objectively because of lack of modern imaging; however, they were reported to have "responses" that enabled resection of axillary and pelvic disease. All four patients with Gardner syndrome experienced disease response. One of these four patients had a complete response twice with doxorubicin-based chemotherapy and eventually died with an ejection fraction of 0.22. Five patients are alive with no evidence of disease (NED), four are alive with disease, and two are lost to follow-up after having an NED status at their last visit. CONCLUSION: The authors conclude that desmoid tumors in adults are responsive to chemotherapy, and such treatment should be considered before embarking on radical treatment to avoid obvious functional consequences and delayed complications.

Adolescent↗
PubMed1993

Dedifferentiated chordoma. Response to aggressive chemotherapy in two cases.

BACKGROUND: Dedifferentiated chordoma is an unusual and aggressive variant of chordoma which is likely to metastasize. Few reports exist of treatment of these tumors with chemotherapy. METHODS: In 1988, two patients with dedifferentiated sacral chordomas were seen at the University of Chicago Hospitals. Both developed metastatic disease less than a year after sacral resection and radiation therapy. These patients' diagnoses, courses, and treatments were reviewed along with the literature on chemotherapy in both conventional and dedifferentiated chordomas. RESULTS: Both patients obtained complete remissions, one to a six-drug regimen and the other to ifosfamide. CONCLUSIONS: A trial of reasonably aggressive chemotherapy is warranted in patients with metastatic dedifferentiated chordoma. The optimum regimen is unclear, but agents active in high-grade sarcomas are logical choices.

Adult↗
PubMed1993

Outpatient treatment of febrile episodes in low-risk neutropenic patients with cancer.

BACKGROUND: Hospitalization and intravenous (IV) broad-spectrum antibiotics are the standard of care for all febrile neutropenic patients with cancer. Recent work suggests that a low-risk population exists who might benefit from an alternate approach. METHODS: A prospective randomized clinical trial was performed comparing oral ciprofloxacin 750 mg plus clindamycin 600 mg every 8 hours with IV aztreonam 2 g plus clindamycin 600 mg every 8 hours for the empiric outpatient treatment of febrile episodes in low-risk neutropenic patients with cancer. RESULTS: The oral regimen cured 35 of 40 episodes (88% response rate), whereas the IV regimen cured 41 of 43 episodes (95% response rate, P = 0.19). Although the cost of the oral regimen was significantly less than that of the IV regimen (P < 0.0001), it was associated with significant renal toxicity (P < 0.05), which led to early termination of the study. Overall, combining its safety and efficacy, the IV regimen was superior (P = 0.03). CONCLUSIONS: This prospective study suggested that outpatient antibiotic therapy for febrile episodes in low-risk neutropenic patients with cancer is safe and effective. Better oral regimens are needed.

Administration, Oral↗
PubMed1993

Cytology of malignant melanoma of soft parts: fine-needle aspirates and exfoliative specimens.

We describe the morphologic features of 25 cytology specimens (13 fine-needle aspirates and 12 exfoliative specimens) obtained from nine patients with malignant melanoma of soft parts (MMSP). Analysis of the fine-needle aspirates and exfoliative specimens revealed primarily a dispersed cell population with occasional cell clustering. Tumor cells were round to polygonal with moderately abundant cytoplasm and had round nuclei with prominent nucleoli. In two cases, an initial definitive diagnosis of MMSP was rendered on material obtained by fine-needle aspiration with the aid of immunocytochemical and ultrastructural studies.

Adolescent↗
PubMed1993

Single-agent ifosfamide studies in sarcomas of soft tissue and bone: the M.D. Anderson experience.

We have used ifosfamide to treat patients with sarcomas in four completed single-agent protocols and one pilot study since 1985. All the studies have used either N-acetyl-L-cysteine (NAC) or mesna as a uroprotective agent, except in one arm of one study where hydration alone was employed. Mesna has proven superior to NAC in providing protection against ifosfamide-induced hematuria. Mesna given as a loading dose followed by continuous 24-h infusion has been effective and most practical in this regard. Ifosfamide has demonstrated clinically useful antitumor activity in our hands against most sarcoma subtypes. Our studies suggest a dose-response relationship for ifosfamide. At a total dose of 6 g/m2 per course, the overall response rate was 10%; at 10 g/m2 per course, it rose to 21%. Future clinical trials will determine ifosfamide's role in combination chemotherapy and more clearly define the best schedule or schedules for the uroprotective administration of mesna.

Acetylcysteine↗
PubMed1992

Preoperative chemotherapy for osteosarcoma with intravenous adriamycin and intra-arterial cis-platinum.

Ninety-seven patients with primary osteosarcoma of the extremities, all age 16 or older, were treated with adriamycin, 90 mg/m2, continuous i.v. infusion over 96 h, followed by cis-platinum, 120-160 mg/m2 by intra-arterial infusion. The first 37 patients, treated from 1979-1982, had a 59% complete response rate and a 54% 5-year continuous disease free survival (CDFS). Patients with complete response had an 85% 5-year CDFS compared with 13% for patients with partial and poor response. Patients treated between 1983-1988 with an intensified regimen have a 68% complete response rate and a 69% 3-year CDFS. Those who did not achieve complete remission were switched to an alternating chemotherapy program emphasizing the use of high-dose methotrexate. Limb salvage has been accomplished in 59% of patients in the first group and 80% in patients of the second group. Preoperative chemotherapy allows informed decisions to be made in postoperative management which can influence overall cure rates. Long-term follow-up is essential before final interpretation of the data.

Bone Neoplasms↗
PubMed1992

Standard and high dose chemotherapy for advanced soft tissue sarcomas.

While significant improvements have been made in the management of localized soft tissue sarcomas, enabling the realization of better functional results and a better overall outcome, progress in metastatic disease has been less than impressive. Adriamycin and DTIC based chemotherapy programs have resulted in response rates of upto 50%, with a small but finite cure fraction, especially in conjunction with surgical resection of residual abnormalities. The decade of the 80s experienced a considerable amount of enthusiasm in exploring the role of ifosfamide and mesna, and identified its definite usefulness as an effective salvage regimen with response rates of approximately 25%-30% in adriamycin failures. Studies evaluating the role of ifosfamide as up-front line agent in combination with adriamycin have met with increased toxicities without a significant additive therapeutic benefit, probably as a result of compromised dose intensity of each individual agent. The steep linear log-dose response relationship of alkylating agents and adriamycin constitutes the theoretical rationale for use of higher doses of chemotherapy, which have become feasible, with the advent of growth factors for bone marrow support. While this approach seems promising in its infancy, with improved complete and overall response, its ultimate effect on survival is anxiously awaited. The limited experience available in the literature with even more aggressive approaches like marrow ablative doses of chemotherapy followed by bone marrow transplantation, have been uniformly disappointing, with extremely short lived responses and extremely high morbidity and cost. As clinical research continues to improve our understanding and ability to implement the currently available therapeutic armamentarium, the search for newer and better drugs needs to continue.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Agents↗
PubMed1992

Phase II study of liposomal muramyl tripeptide in osteosarcoma: the cytokine cascade and monocyte activation following administration.

PURPOSE: A phase II trial that uses liposome-encapsulated muramyl tripeptide phosphatidylethanolamine (L-MTP-PE) in patients with relapsed osteosarcoma is underway. To determine if in vivo cytokine induction plays a role in the mechanism of action of L-MTP-PE, we investigated the circulating cytokine levels of 16 patients who were undergoing therapy. PATIENTS AND METHODS: Patients had histologically proven osteosarcoma and pulmonary metastases that developed either during adjuvant chemotherapy or that were present at diagnosis and persisted despite chemotherapy. Patients were rendered disease-free by surgery. The major goal of the study was to improve the disease-free interval in this high-risk group. L-MTP-PE 2 mg/m2 was infused during a 1-hour period twice a week for 12 weeks, then once a week for 12 weeks. Serial blood samples were collected after L-MTP-PE administration and were assayed for cytokine levels (tumor necrosis factor-alpha [TNF alpha] interleukin-1 alpha [IL-1 alpha], IL-1 beta, IL-6, interferon-gamma [IFN-gamma], neopterin, C-reactive protein). RESULTS: After the infusion of L-MTP-PE, there was rapid induction of circulating TNF alpha and IL-6. TNF alpha levels peaked 1 to 2 hours after infusion in 10 of 16 patients, whereas peak IL-6 levels were detected at 2 to 3 hours in all patients. Induction of circulating TNF alpha and IL-6 was evident only after the first dose of L-MTP-PE. Neither IL-1 alpha nor IL-1 beta was detected in the plasma. Neopterin levels increased at 24 hours postinfusion, which indicated macrophage activation, and were not related to the induction of circulating IFN-gamma. C-reactive protein was elevated in all patients at 24 hours and decreased by 72 hours. Unlike circulating TNF alpha and IL-6, elevations in C-reactive protein and neopterin could be detected throughout the treatment course. CONCLUSION: It is concluded that L-MTP-PE has specific biologic effects in patients with osteosarcoma that may be important to the drug's immunostimulatory capacity and its effectiveness as an antitumor agent.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1991

Phase III comparison of doxorubicin and dacarbazine given by bolus versus infusion in patients with soft-tissue sarcomas: a Southwest Oncology Group study.

Disseminated soft-tissue sarcomas are a group of uncommon malignancies generally treated in a uniform manner. This study questioned the impact of schedule on response rate and toxicity in patients with metastatic soft-tissue sarcoma treated with the two-drug combination doxorubicin and dacarbazine. Patients were randomly assigned to receive either bolus therapy with doxorubicin at a dose of 60 mg/m2 and dacarbazine at a dose of 750 mg/m2 intravenously on day 1 (118 patients) or infusional therapy with doxorubicin at 60 mg/m2 and dacarbazine at 750 mg/m2 delivered by continuous intravenous infusion for 96 hours on days 1-4 (122 patients). Chemotherapy was to be repeated every 3 weeks. A unique feature of this cooperative group protocol was a provision for surgical resection of residual disease in patients with a partial response or with stable disease following chemotherapy. Similar overall response rates (17% in both treatment arms) and complete response rates (5% in both treatment arms) were observed. For patients receiving bolus therapy, the median response duration was 19.6 months for those in complete remission and 6.6 months for those in partial remission. For patients receiving infusional therapy, the median response duration was 12.6 months for those in complete remission and 9.3 months for those in partial remission. Examination of dose intensity received when combining treatment arms revealed a weak doxorubicin dose-response relationship. There was no difference in median survival times between the two treatment arms (bolus therapy, 10.6 months; infusional therapy, 10.5 months; logrank P = .97). Analysis of toxic effects favored infusional therapy. Significant reductions in cardiac toxicity (all events, P = .04; clinical events, P = .01) and nausea and emesis (P = .04) were seen in infusional therapy. Of 47 patients eligible for cytoreductive surgery following chemotherapy, 12 received surgery, and of those 12, eight were rendered disease free. The use of a 96-hour continuous intravenous infusion of doxorubicin-dacarbazine was comparable therapeutically with bolus dosing of these two agents and was better tolerated by the patients.

Adolescent↗