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R J Amato

Publications and source records attributed to R J Amato.

At least 37 records · Page 2Linked to original sources
PubMed1998

Metastatic small-cell carcinoma of the prostate diagnosed by fine-needle aspiration biopsy.

Fourteen fine-needle aspiration biopsies (FNABs) of metastatic small-cell carcinoma done on 12 patients who had histologically documented primary small-cell carcinoma of the prostate are described. The FNABs were of lymph node (four cases), liver (four cases), bone (two cases), pancreas (one case), perirectal soft tissue (one case), perineum (one case), and lung (one case). One patient underwent three FNABs. No patient had a second primary tumor elsewhere. Cytologic smears were cellular with numerous single tumor cells, many apoptotic bodies, and variable numbers of mitotic figures. Tight cell clusters with molded nuclei and finely stippled chromatin were seen in all cases. An organoid pattern of tumor cells was seen focally in two cases. Features distinguishing small-cell carcinoma from poorly differentiated prostate carcinoma were cell size, finely stippled chromatin, inconspicuous nucleoli, and numerous single tumor cells. Distinction from small-cell carcinoma of other primary sites requires clinical and radiologic correlation. We conclude that cytologic specimens are useful for documenting metastatic small-cell carcinoma of the prostate and for differentiating between it and conventional prostate carcinoma in metastatic sites.

Aged↗
PubMed1998

Primary malignant teratoma of the thyroid gland: report and discussion of two cases.

BACKGROUND: Teratoma of the thyroid in adults is a rare neoplasm and is usually seen in young females. Most of the thyroid teratoma are malignant. The tumor appears as a dominant mass in the thyroid gland and is often associated with local lymph node involvement. We describe our experience of primary malignant teratoma of the thyroid in two young women who were treated with aggressive chemotherapy and surgical intervention. METHODS: Medical records of two patients treated between 1993 and 1995 were reviewed. Both patients were women (36 years old and 34 years old). The diagnosis of primary malignant teratoma of the thyroid was made on the basis of clinical, radiographic, and microscopic findings. Patients were treated with aggressive combination chemotherapy consisting of alternating regimens similar to those used for high-volume germ-cell tumor patients at the University of Texas M. D. Anderson Cancer Center. RESULTS: One of the patients demonstrated a partial response to chemotherapy and underwent postchemotherapy surgery for removal of residual disease. The other patient had a complete response to chemotherapy. Both patients are alive and disease free for 32- and 26-plus months. CONCLUSIONS: Primary malignant teratoma of the thyroid is sensitive to combination chemotherapy. It appears that the treatment strategy offered-aggressive induction chemotherapy with planned surgery for removal of residual disease, similar to that for patients with testicular tumors-has the potential to provide a durable, complete remission.

Adult↗
PubMed1998

Phase I study of suramin combined with doxorubicin in the treatment of androgen-independent prostate cancer.

In this study, we determined the maximum tolerated plasma concentration of suramin (within the predetermined study target range) when combined with doxorubicin in the treatment of androgen-independent prostate cancer. Twenty-four patients received suramin dosages based on proportional adjustment of the steady-state plasma suramin concentration to achieve the targeted plasma concentrations of 50-100, 101-150, 151-200, or 201-250 microg/ml. Doxorubicin (20 mg/m2) was administered i.v. over 24 h at weekly intervals. Suramin was given i.v. over 2 h twice weekly. Patients received treatment until dose-limiting toxicity or disease progression. Side effects similar to those reported for suramin and doxorubicin administered as individual agents were observed. Dose-limiting motor neuropathy developed in three patients (13%). Twelve of 24 evaluable patients (50%; 95% confidence interval, 28-71%) and 6 of 10 evaluable patients (60%; 95% confidence interval, 26-88%) had a >50% decrease of prostate-specific antigen and measurable lesions, respectively. The maximum tolerated plasma level of suramin when combined with doxorubicin was 151-200 microg/ml. Future studies on suramin combined with doxorubicin or other agents could be performed using a fixed dosing scheme with a targeted suramin steady-state plasma concentration of 200 microg/ml.

Adult↗
PubMed1998

Dose intensity: its limitation and the M. D. Anderson Cancer Center's view of its application.

Therapy for germ cell tumors has been viewed as a model of successful treatment development in solid tumors. Despite this, treatment remains unsatisfactory in patients with poor risk or high volume at initial presentation. Present strategies under investigation include the use of dose intensification through the shortening of treatment intervals and the dose escalation of agents with a presumed dose-response relationship in the presence or absence of bone marrow transplant or stem cell support.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Combination chemotherapy for metastatic or locally advanced genitourinary squamous cell carcinoma: a phase II study of methotrexate, cisplatin and bleomycin.

PURPOSE: The prognosis of patients with advanced squamous cell carcinoma of genitourinary origin is poor. While single agent chemotherapy results mainly in partial responses of short duration, data on the efficacy of combination chemotherapy are extremely limited. We determined the response rate and toxicity of a combination of 3 of the most active agents, methotrexate, cisplatin and bleomycin, in patients with advanced genitourinary squamous cell carcinoma. MATERIALS AND METHODS: Patients with metastatic or locally advanced genitourinary squamous cell carcinoma were eligible for study. Treatment consisted of 200 mg./m.2 methotrexate on days 1, 15 and 22, and 20 mg./m.2 cisplatin and 10 mg./m.2 bleomycin on days 2 through 6 during a 28-day cycle. RESULTS: Of the 30 patients who enrolled in the trial 29 were evaluable for response. Objective response was achieved in 16 patients (55%, 95% confidence interval 36 to 72), 4 of whom achieved a complete response (14%). Median objective response duration was 4.7 months (range 1.9 to 39.5). Median survival of the entire group was 11.5 months (range 1.5 to 87.0). Of the patients 9 achieved disease-free status, including 6 following consolidation surgery or radiation therapy. Median survival of these 9 patients (34.4 months, range 9.6 to 87.0) was significantly greater (p = 0.0003) than that of patients who did not become disease-free (7.0 months, range 1.5 to 38.6). Grade III or IV hematological toxicity in 116 courses included neutropenia (13%) and thrombocytopenia (6%). Among 30 patients evaluable for toxicity serious nonhematological toxic effects included stomatitis (3%) and renal toxicity (7%). There was 1 death from neutropenic sepsis. CONCLUSIONS: Methotrexate, cisplatin and bleomycin combination chemotherapy for genitourinary squamous cell carcinoma results in a high but short lived overall response rate, and a low complete response rate with manageable toxicity. A multidisciplinary approach to achieve disease-free status may provide the best opportunity to effect survival and should be the focus of future trials.

Adult↗
PubMed1997

Phase II trial of 5-fluorouracil, interferon-alpha and continuous infusion interleukin-2 for patients with metastatic renal cell carcinoma.

BACKGROUND: This study was designed to evaluate the efficacy and toxicity of the combination of 5-fluorouracil, interferon-alpha, and interleukin-2 for patients with metastatic renal cell carcinoma. METHODS: Previously untreated patients with a Zubrod performance status of < or =2; adequate cardiac, pulmonary, and renal function; and absence of brain metastases were eligible. One course of therapy was 28 days. 5-fluorouracil was administered at a dose of 600 mg/m2/day as a continuous infusions on Days 1-5. Interleukin-2 also was administered as a continuous infusion on Days 1-5 at a dose of 2 million Roche U/m2/day. Interferon-alpha was given as a daily subcutaneous injection of 4 million U/m2/day. RESULTS: Fifty-five patients were enrolled in the trial and 52 were evaluable for response. All patients experienced fever and flu-like symptoms. Grade 3 or 4 nonhematologic toxic effects included hypertension (48%), dermatitis (12%), stomatitis (11%), and altered mental status (9%). There was one toxic death. Four complete responses and 12 partial responses were observed for a total response rate of 31% (95% confidence interval, 18-46%). The survival of responding patients was significantly better than that of nonresponding patients. The improvement in survival was even more significant when comparing patients with at least stable disease with those who progressed through treatment. CONCLUSIONS: The three-drug combination described in this study demonstrates activity. However, it appears to be more toxic than other regimens with similar response rates and cannot be recommended for standard practice. Changing the interleukin-2 route to subcutaneous administration may permit more continuous administration with less toxic effects.

Adult↗
PubMed1997

Phase II trial of alternating weekly chemohormonal therapy for patients with androgen-independent prostate cancer.

Two distinct regimens of weekly chemotherapy for hormone-refractory prostate cancer were combined in an alternating schedule and tested in a Phase II trial to determine efficacy and toxic effects. Forty-six patients with hormone-refractory prostate cancer and rising prostate-specific antigen (PSA) levels entered the trial. Therapy consisted of doxorubicin (20 mg/m2/week) plus oral ketoconazole (400 mg three times a day) given at weeks 1, 3, and 5 and vinblastine (5 mg/m2/week) plus oral estramustine (140 mg three times a day) given at weeks 2, 4, and 6. No therapy was given at weeks 7 and 8. Replacement doses of hydrocortisone were administered throughout treatment to counteract potential adrenal insufficiency secondary to the ketoconazole. In 67% of patients (31 of 46), the PSA declined by 50% or greater for a minimum duration of 8 weeks (95% confidence interval, 52-80%). Among the 16 patients with measurable soft tissue disease, there were 12 responses (75%; 95% confidence interval, 47-92%). The median duration of response was 8. 4 months (1.8-14.9). The median survival for the entire group was 19 months. The median survival of PSA responders has not been reached, whereas that of nonresponders was 13 months (P = 0.010). Seventy-six percent of symptomatic patients noted improvement. Hematological toxicity was modest and was managed without growth factors. Peripheral edema (49%) and deep venous thrombosis (18%) were the most common nonhematological toxicities. The alternating weekly regimen of chemohormonal therapy is active for hormone-refractory prostate cancer, providing a high rate of symptom control, soft tissue response, and PSA decline.

Anti-Inflammatory Agents↗
PubMed1996

Intraabdominal desmoplastic small cell tumor. Report and discussion of five cases.

BACKGROUND: Intraabdominal desmoplastic small cell tumor is a rare malignancy that has only recently been described. In the adult population, it is usually seen in young males. The tumor appears to arise as a dominant mass or masses in the abdominal cavity, particularly in the pelvic region, without a clear visceral origin. Multiple small tumor nodules may be found attached to the peritoneal surface. Visceral metastases occur late in the clinical course, ultimately leading to the patient's death. Five young adults with intraabdominal desmoplastic small cell tumors were treated with aggressive chemotherapy. METHODS: Charts of five patients treated between 1990 and 1995 were reviewed. The diagnosis of desmoplastic small cell tumor was made on the basis of typical clinical and radiographic findings, light microscopy showing hyperchromatic cells surrounded by a desmoplastic stroma, and immunohistochemistry demonstrating markers of epithelial and mesenchymal differentiation. Patients were treated with aggressive combination chemotherapy consisting of alternating regimens similar to those used as testis cancer salvage therapy. RESULTS: Four of the five patients demonstrated a partial response to chemotherapy. Two of the responding patients had surgery with the intent of removing all residual disease, but this was successful in only one case. All patients have died from their cancer. CONCLUSIONS: Intraabdominal desmoplastic small cell tumors are sensitive to combination chemotherapy. It appears that treatment offers good palliation and may prolong survival in isolated cases. However, even the patients managed with the most aggressive medical and surgical approaches are not cured and ultimately die of their disease.

Abdominal Neoplasms↗
PubMed1996

What does the pathology report really mean?

The correct histological diagnosis, the extent of the tumor, and the histological variables that affect prognosis are important in selecting the initial treatment and determining the need for and type of additional therapy. Therefore, a pathology report should include the following information: (1) histological classification, seminoma versus nonseminomatous germ cell tumor, including the percentage of germ cell components for the latter; (2) presence of vascular and/or lymphatic invasion; (3) involvement of spermatic cord or epididymis; (4) status of cord margin of resection; and (5) a statement about whether viable carcinoma or teratomatous elements are present in the metastatic specimen after chemotherapy. For nonseminomatous germ cell tumors, the pathology report should include a statement about whether the tumor is pure or mixed, and if the latter, the relative amount of each component.

Adult↗
PubMed1995

Fine-needle aspiration cytology of seminoma: a review of 16 cases.

We report the cytomorphologic features of 16 fine-needle aspiration (FNA) biopsies of seminoma obtained from 16 male patients. The aspirates included two primary gonadal tumors (one occurring in a cryptorchid testis), two primary mediastinal tumors, and 12 metastases (two with unknown primaries). Analysis of the aspirates revealed a primarily dispersed cell population of large cells with scant to moderately abundant cytoplasm. The nuclei were round to slightly irregular, had finely granular chromatin, and had either one central prominent nucleolus or two to three smaller nucleoli. Variable numbers of lymphocytes and plasma cells were intermingled with the tumor cells. Only a few cases had epithelioid histiocytes or the characteristic "tigroid" background. The cytologic features of the metastases were distinctive and were considered diagnostic for therapeutic management. In six cases, an initial diagnosis of seminoma by FNA biopsy identified the neoplasm as germ cell in origin rather than other neoplasms in the differential diagnosis, thereby expediting therapeutic management.

Adult↗
PubMed1995

Carboplatin and ifosfamide and selective consolidation in advanced seminoma.

This prospective phase II study assesses the clinical efficacy and complications of a treatment regimen comprising combination chemotherapy with carboplatin and ifosfamide and selective consolidation in advanced seminoma. Of 43 patients who entered the study, between May 1989 and May 1992, 42 were evaluable. 30 achieved a complete remission (71%; 95% confidence interval, 56-84%) after chemotherapy alone. 10 achieved a complete remission (24%; 95% confidence interval, 13-39%) after chemotherapy plus consolidation. 38 of the 42 patients (91%; 95% confidence interval, 83-98%) remained in remission after a median follow-up period of 35 months (20-56 months). No patient experienced nephrotoxic, neurotoxic, or ototoxic effects, or haemorrhagic cystitis. Ten per cent of the patients had leucopenic fever requiring hospitalisation. Twenty-four per cent required platelet transfusions, and 26% required transfusions of packed red blood cells. For patients with seminoma, treatment with carboplatin and ifosfamide and selective consolidation is safe and effective.

Adolescent↗
PubMed1995

Escalated MVAC with or without recombinant human granulocyte-macrophage colony-stimulating factor for the initial treatment of advanced malignant urothelial tumors: results of a randomized trial.

PURPOSE: Hematopoietic growth factors have been shown to ameliorate the side effects of chemotherapy. Here we assess the ability of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) to increase the dose-intensity and reduce the side effects of escalated methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) chemotherapy. PATIENTS AND METHODS: A prospective randomized trial to compare escalated MVAC versus escalated MVAC with rhGM-CSF was conducted. All patients were treated at The University of Texas M.D. Anderson Cancer Center (UTMDACC) and had a metastatic or unresectable urothelial tumor. Forty-eight patients were randomized (25 to MVAC with rhGM-CSF and 23 to escalated MVAC alone). The clinical characteristics of the study populations were similar (ie, degree of tumor dissemination and performance status). RESULTS: The dose-intensity in the two arms of the study did not differ significantly. No difference in the frequency of bacteriologically documented infections occurred between the two study arms. CONCLUSION: The use of the hematopoietic growth factor rhGM-CSF did not result in an increased dose-intensity of escalated MVAC. The inability to increase the dose-intensity of MVAC further was a result of nonhematologic side effects of the chemotherapy. Escalation of treatment delivered at its median-tolerated dose is unlikely to result in additional therapeutic benefit for patients with common solid tumors. Future development of therapy may require the development of new agents or concepts, rather than modification of existing therapies.

Adult↗
PubMed1994

Phase II trial of low dose gamma-interferon in metastatic renal cell carcinoma.

We conducted a phase II trial to confirm the activity of fixed, low dose gamma-interferon in metastatic renal cell carcinoma. A total of 35 patients with metastatic renal cell carcinoma, who had not received prior immunotherapy and who had a Zubrod performance status of 2 or less, was enrolled in this study. Primary tumors were controlled by nephrectomy or embolization before treatment began. gamma-Interferon was administered weekly as a subcutaneous injection at a fixed dose of 100 micrograms. Toxic effects were limited to low grade fever, chills and myalgias within 24 hours of injection. There were no incidences of grade 3 or 4 toxicity. Responses could be evaluated in 34 patients. There were 1 complete and 4 partial responses, for an objective response rate of 15% (95% confidence interval 5 to 32%). Durations of response to date are 21+, 17+, 13+, 9 and 2 months. We conclude that gamma-interferon is an active agent for metastatic renal cell carcinoma when administered according to this dose and schedule. The response rate compares favorably with those of alpha-interferon and interleukin-2, and toxicity is minimal. gamma-Interferon has excellent potential for use in combination with other biological or chemotherapeutic agents and in the adjuvant setting.

Adult↗
PubMed1994

Phase I study of interleukin-2 combined with interferon-alpha and 5-fluorouracil in patients with metastatic renal cell cancer.

Interferon-alpha (IFN-alpha) and interleukin-2 (IL-2) each has produced a 15%-20% response in metastatic renal cell cancer. Combining IFN-alpha with either IL-2 or 5-fluorouracil (5-FU) enhanced IFN-alpha activity. We have therefore conducted a Phase I Study combining IL-2, IFN-alpha, and 5-FU. The patients were continuously infused with IL-2 (1-3 x 10(6) u/m2) and 5-FU (600-750 mg/m2) for a 5-day period every 28 days, and IFN-alpha (4-5 x 10(6) u/m2) was injected subcutaneously daily. Lymphokine-activated killer (LAK) and natural killer (NK) cell activity was measured on days 0 and 8. Twenty-one patients received 76 courses. All primary tumors were controlled by surgery (81%) or angioinfarction. Hematologic toxicity was mild; median nadir of platelets was 117 K/microL and of granulocytes was 1.2 K/microL. Dose-limiting toxicity included mucositis, liver damage, and hypotension. No treatment-related death occurred, and only one patient required intensive-care-unit support. Two patients had an objective response, one of which was a complete response. Increased LAK cell and NK cell activity occurred at all IL-2 dose levels. Simultaneous delivery of IL-2, IFN-alpha, and 5-FU is safe and shows antitumor and biologic activity. 5-FU did not appear to suppress IL-2-induced LAK and NK cell activation. Maximum tolerated dose of the three-drug combination is IL-2, 2 x 10(6) u/m2, 5-FU 600 mg/m2, and IFN-alpha, 4 x 10(6) u/m2.

Adult↗
PubMed1993

Fine-needle aspiration of intra-abdominal desmoplastic small cell tumor.

The cytologic features of four cases of histologically confirmed intra-abdominal desmoplastic small cell tumor (DSCT) that occurred in males between 18-27 yr of age are presented. Smears showed small cells with scant cytoplasm which were primarily arranged in loosely cohesive clusters. Nuclei were oval to round with evenly distributed, finely granular chromatin and inconspicuous nucleoli. As is typical of DSCT, the cells strongly expressed keratin and desmin in all cases. In the one case studied by electron microscopy, it was demonstrated that the cells were joined by small junctions and contained paranuclear aggregates of intermediate filaments. The absence of the characteristic desmoplastic stroma in DSCT aspirates and the nonspecific cytologic features of this small round-cell tumor (SRCT) made cytologic interpretation difficult. Cytopathologists should be aware of this entity so that DSCT is included in the differential diagnosis of SRCTs that occur in intra-abdominal sites. A panel of markers that includes keratin and desmin should be used to assist in the identification of DSCT.

Abdominal Neoplasms↗
PubMed1993

Surgery following response to interferon-alpha-based therapy for residual renal cell carcinoma.

The role of aggressive surgery for metastatic renal cancer in the era of biological therapy is not clear. Therefore, we reviewed 17 patients who, between February 1987 and August 1990, underwent surgical resection of residual masses following initial response to interferon-alpha-based therapy. Viable tumor persisted in 15 patients (88%), whereas only inflammatory response was detected in 2. Of the patients 11 (65%) remained disease-free at a median of 12 months postoperatively (range 5 to 29), with an overall median survival of 26 months (range 6 to 34) from treatment initiation. These data suggest that surgery may be of therapeutic benefit in select patients with renal cell carcinoma who do not meet traditional criteria for surgical resection. Prospective trials are being performed to determine whether there is a role for aggressive surgical resection of persistent disease in patients with advanced renal cell carcinoma who have previously responded to interferon-alpha-based therapy.

Adult↗
PubMed1992

Chemotherapy for small cell carcinoma of prostatic origin.

A total of 21 patients with metastatic small cell carcinoma of the prostate was treated with combination chemotherapy, either following initial hormonal therapy (15) or as initial therapy (6). Of the patients 13 (62%) had pure small cell carcinoma, whereas 8 (38%) had mixed histology of small cell carcinoma and adenocarcinoma. Patients presented with a characteristic clinical picture of a large primary mass (16 cases) with a high frequency of visceral metastases to the liver (9), lungs (7) and brain (2). The majority of the patients did not have an elevated serum prostate specific antigen (1 of 14, 7%) or prostatic acid phosphatase (2 of 21, 10%). Serum carcinoembryonic antigen was elevated in 13 patients (62%). Of the 21 patients 13 (62%) responded to chemotherapy. Survival after the diagnosis of small cell carcinoma of the prostate resulted in a median of 9.4 months with a range of 1 to 25 months. The regimens used were those considered active in the treatment of small cell carcinoma of the lung (vincristine, doxorubicin and cyclophosphamide, or etoposide and cisplatin with or without doxorubicin). Small cell carcinoma of the prostate has a characteristic clinical picture and a high response rate to cytotoxic therapy. Early introduction of chemotherapy in the treatment of small cell carcinoma of the prostate may increase the survival rate.

Aged↗