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Biomedical subjects

R J Motzer

Publications and source records attributed to R J Motzer.

At least 109 records · Page 6Linked to original sources
PubMed1992

High-dose chemotherapy and autologous bone marrow rescue for patients with refractory germ cell tumors. Early intervention is better tolerated.

Therapy with high-dose carboplatin plus etoposide-based chemotherapy plus autologous bone marrow rescue (AUBMR) was administered to 29 patients with advanced germ cell tumors (GCT) refractory to cisplatin-based chemotherapy. Two groups of patients with refractory disease were treated. Sixteen patients had been identified as "poor risk" at diagnosis and had an inappropriately slow decline of serum tumor markers after two cycles of induction cisplatin-based therapy (Group A). In addition, 13 patients were treated who had never had a complete response (CR) or had relapses after ifosfamide-based salvage chemotherapy (Group B). Patients in Group A were treated with high-dose carboplatin etoposide, and patients in Group B received high-dose carboplatin, etoposide, and cyclophosphamide. Fifteen of 29 (52%) patients had a CR (9, Group A; 6, Group B). The patients in Group A had fewer hematologic toxic effects, and the median number of days from day 0 to a granulocyte count greater than 0.5/microliters was 16 and to a platelet count of more than 50/microliters was 15, compared with 22 days and 23 days in Group B, respectively. There were fewer episodes of culture-positive sepsis in Group A (12%) compared with Group B (26%), and the only treatment-related death occurred in Group B. Therapy with high-dose carboplatin plus etoposide-based chemotherapy plus AUBMR is effective for patients with GCT refractory to regimens of cisplatin with or without ifosfamide. Early use of high-dose chemotherapy reduces hematologic toxic effects and allows patients to start treatment in a more predictable fashion after cytoreduction, rather than when the disease is progressing rapidly.

Adult↗
PubMed1992

Phase II study of iproplatin (CHIP) in patients with cisplatin-refractory germ cell tumors; the need for alternative strategies in the investigation of new agents in GCT.

Fifteen patients with advanced, cisplatin-refractory germ cell tumors (GCT) were treated with iproplatin (CHIP). No objective responses were noted in any of the patients treated. By restricting the entry criteria to heavily pre-treated patients, the identification of new active agents in phase II trials may be hindered. Alternative strategies for the investigation of new agents in patients with GCT should be considered, particularly when studying the efficacy and relative toxicity of platinum analogues.

Antineoplastic Agents↗
PubMed1992

t(12;22)(q13;q13) and trisomy 8 are nonrandom aberrations in clear-cell sarcoma.

We report a case of clear-cell sarcoma with a t(12;22)(q13;q13) and multiple copies of chromosome 8 in addition to other abnormalities. An identical or similar translocation has previously been reported in this type of tumor, suggesting that the t(12;22) is a primary cytogenetic change in the pathogenesis of a subset of clear-cell sarcomas. In addition, the presence of extra copies of chromosome 8, commonly noted in our case and others, suggests that it represents a nonrandom secondary change in these tumors.

Chromosome Aberrations↗
PubMed1992

Distribution of retroperitoneal metastases after chemotherapy in patients with nonseminomatous germ cell tumors.

For patients with advanced nonseminomatous germ cell tumors a retroperitoneal lymph node dissection is routinely performed following chemotherapy if the serum tumor markers have returned to normal. Bilateral retroperitoneal lymph node dissection has been recommended because metastatic deposits may be widespread. The aim of this study was to describe the distribution of retroperitoneal metastases following chemotherapy in patients with nonseminomatous germ cell tumor and determine if the extent of the retroperitoneal lymph node dissection can be modified. We studied 113 patients who had initially bulky retroperitoneal disease and underwent retroperitoneal lymph node dissection following chemotherapy. For the purposes of this study teratoma and malignant germ cell tumor are referred to as tumor. The most common location of tumor was the para-aortic area (91%) in patients with a left primary tumor and the interaortocaval area (78%) in those with a right tumor. Tumor was located outside the boundaries of a modified retroperitoneal lymph node dissection in 14 of the 60 patients with residual disease but the tumor was present within a palpable mass in 6 of these 14 patients. If the residual mass was removed and a modified retroperitoneal lymph node dissection was performed only 9 of the 113 patients (8%) would have tumor left in the retroperitoneum. For a select group of patients with advanced nonseminomatous germ cell tumor treated with chemotherapy, resection of the residual mass combined with modified retroperitoneal lymph node dissection is appropriate.

Humans↗
PubMed1992

A phase II trial of interleukin-2 and interferon alfa-2a in patients with advanced renal cell carcinoma.

PURPOSE: A phase II trial that used a regimen of interleukin-2 (IL-2) and interferon alfa-2a (IFN-alpha) was undertaken to evaluate the efficacy of this combination in the treatment of metastatic renal cell carcinoma. PATIENTS AND METHODS: Thirty-four assessable patients were treated with one to two induction cycles of IL-2 administered by continuous intravenous (IV) infusion at a dose of 3 x 10(6) U/m2/d [corrected] for 4 days per week plus IFN-alpha administered by subcutaneous injection at a dose of 5 x 10(6) U/m2/d [corrected] for 4 days per week for 3 consecutive weeks. A maintenance regimen of IL-2 2 x 10(6) U/m2/d [corrected] given by continuous IV infusion for 5 days per week plus IFN-alpha subcutaneously at a dose of 6 x 10(6) U/m2/d [corrected] that was given 3 days per week for 3 weeks was administered for one to five cycles. Twenty-eight patients (82%) completed one to two induction cycles, and 14 patients (41%) received maintenance doses. RESULTS: Major responses were achieved in four patients (12%), which included one complete response (CR) in a bone metastasis. Responses were observed in patients both with and without prior nephrectomy as well as in a primary tumor. Toxicity was moderately severe and included two treatment-related deaths. CONCLUSIONS: In view of the minimal antitumor activity and associated toxicity, the combination of IL-2 and IFN-alpha in this trial cannot be recommended. The investigation of new cytokines and the identification of biologic prognostic factors for a response to immunologic therapy are essential.

Adult↗
PubMed1992

Ifosfamide-based chemotherapy for patients with resistant germ cell tumors: the Memorial Sloan-Kettering Cancer Center experience.

Sixty-six patients with germ cell tumors (GCTs) refractory to cisplatin plus etoposide/vinblastine-based therapy were treated with cisplatin, ifosfamide, and either etoposide (VIP) (50 patients) or vinblastine (VeIP) (16 patients). Sixty-two patients were evaluable for response. Twenty-one patients (34%) achieved a complete response (CR), 18 with chemotherapy alone and an additional three following surgical resection of viable tumor. Six of these patients have relapsed, and 15 (24%) remain in CR at a median follow-up of 13 months (range, 3+ to 41+ months). Three patients who achieved an incomplete response or relapsed from CR are disease free following additional salvage therapy; one patient underwent resection of a solitary metastasis and two received high-dose chemotherapy with autologous bone marrow rescue. Ifosfamide adds efficacy to cisplatin plus etoposide or vinblastine-based salvage therapy. Ifosfamide/cisplatin-based combinations should be considered in the first-line salvage treatment of germ cell tumors. The modest proportion of patients who achieve a durable CR following salvage therapy with VIP/VeIP emphasizes the need for early identification of treatment failure and more effective salvage therapy.

Adult↗
PubMed1992

Current perspectives on the role of adjunctive surgery in combined modality treatment for patients with germ cell tumors.

The role of surgery in patients with advanced GCT after chemotherapy has evolved substantially in the era of combined modality therapy. In evaluating patients for surgery after chemotherapy, the clinician must consider carefully the histology (seminoma v NSGCT) of the primary as well as the extent of the residual disease. In patients with seminoma, the size of residual disease (greater than or equal to 3 cm) permits selection of patients with a high incidence of residual malignancy. In contrast, criteria designed to select NSGCT patients in whom surgical intervention after chemotherapy can be avoided are associated with substantial error. A normal radiographic evaluation in patients with NSGCT does not indicate a negative pathology and the treating physician must consider the approximately 20% risk of residual teratoma or carcinoma despite evidence of a radiographic CR. Continued research is needed to improve the sensitivity and specificity of case selection for patients requiring surgery after chemotherapy in order to limit the toxicity of curative therapy in this patient population.

Antineoplastic Combined Chemotherapy Protocols↗
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

Salvage chemotherapy for patients with germ cell tumors. The Memorial Sloan-Kettering Cancer Center experience (1979-1989).

Twenty-eight of 124 (23%) advanced germ cell tumor (GCT) patients who were treated on four successive platin-based induction regimens and who failed to achieve a durable complete response (CR) remain alive (median follow-up, 50 months). An analysis of prognostic factors for response and survival was conducted on the 94 patients who received salvage chemotherapy. Survival and/or response to salvage therapy were significantly enhanced for patients with a prior CR to induction chemotherapy, treatment with a cisplatin-based salvage regimen, a testis primary site, a normal serum human chorionic gonadotropin level, a normal serum lactate dehydrogenase level, one site of metastasis, and an Indiana Class of 6 or less. Patients with a prior incomplete response (IR) had a particularly poor prognosis (P = 0.00007) with only 4 of 52 (9%) patients alive (median follow-up, 37 months) compared with 15 of 42 (36%) patients with a prior best response of a CR (median follow-up, 35 months). The poor survival of patients who fail to achieve a durable CR to induction chemotherapy warrants the continued investigation of new salvage therapy. The identification of prognostic features may direct salvage therapy and aid in the interpretation of clinical trials of salvage regimens.

Adolescent↗
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

The effect of a 7-day delay in chemotherapy cycles on complete response and event-free survival in good-risk disseminated germ cell tumor patients.

The effect of duration of induction treatment on complete response (CR) and event-free survival (EFS) (time to death or relapse) was evaluated in 162 "good-risk" germ cell tumor (GCT) patients treated from November 1982 to July 1986 in a randomized prospective trial with VAB-6 (cyclophosphamide + vinblastine + bleomycin + dactinomycin + cisplatin; 81 patients) versus etoposide + cisplatin (EP; 81 patients). Patients received three cycles of VAB-6 every 28 days or four cycles of EP every 21 days. Treatment cycle with either regimen was routinely postponed for 7 days for leukocytes less than 3000/mm3 or platelets less than 100,000/mm3 and then administered regardless of blood count. The number of treatment days was calculated for each patient from initial treatment day to final induction date plus 28 days for VAB-6 and plus 21 days for EP. The proportion of CR and the EFS for good-risk GCT patients treated with cisplatin-based chemotherapy were not influenced by a less than or equal to 7-day delay resulting from chemotherapy-induced myelosuppression. Short, planned delays in chemotherapy for good-risk GCT patients (less than or equal to 7 days per cycle) appear to be acceptable since they may prevent serious toxicity in this curable patient population. Delays of longer than 7 days are strongly discouraged except in extraordinary life-threatening circumstances.

Adolescent↗
PubMed1990

Carboplatin, etoposide, and bleomycin for patients with poor-risk germ cell tumors.

A prospective study of four cycles of carboplatin (CBDCA) + etoposide + bleomycin (EBC) was conducted in 32 previously poor-risk nonseminomatous germ cell tumor (GCT) patients and the results compared with past studies. Patients with extragonadal (nine patients) and testicular nonseminomatous GCT with a probability of complete response (CR) less than 0.5 as calculated by a mathematical model using marker values and number of metastatic sites (23 patients) were included. Nineteen patients (59%) achieved a CR and 14 complete responders (43%) remain free of disease. The overall and durable CR proportions were similar to those observed in prior poor-risk studies at Memorial Sloan-Kettering Cancer Center. Myelosuppression was the major toxicity. Based on the low CR proportion, EBC is no better than other standard programs for poor-risk GCT. However, its ease of administration as an outpatient, mild renal and gastrointestinal toxicity, and efficacy comparable to cisplatin-based chemotherapy used in prior poor-risk trials at Memorial Sloan-Kettering Cancer Center warrant a Phase III trial comparing CBDCA-based and cisplatin-based chemotherapy for good-risk GCT patients.

Adolescent↗
PubMed1990

Cytogenetic and immunohistochemical evidence for the germ cell origin of a subset of acute leukemias associated with mediastinal germ cell tumors.

Most acute leukemias occurring in patients with mediastinal germ cell tumors (MGCTs) appear to be primary rather than therapy-related; however, no data have been obtained to date to confirm the hypothesized germ cell origin of the leukemias in this syndrome. We identified six male patients with this syndrome treated at Memorial Sloan-Kettering Cancer Center: in all six, the leukemia was studied immunohistochemically for various hematologic and germ cell antigens; in four, the karyotype of the leukemia was available; in one, the MGCT had also been karyotyped. In three patients, we found evidence of a germ cell origin of the acute leukemias. A 19-year-old male developed an acute myeloblastic leukemia 11 months after presenting with an MGCT; karyotypes of the two tumors showed them to be clonally related, both showing an i(12p), a cytogenetic marker of germ cell tumors. A 16-year-old male with probable Klinefelter's syndrome presented simultaneously with acute monocytic leukemia and an MGCT; although the MGCT was not karyotyped, the leukemia showed an i(12p). A 23-year-old male developed concurrently an MGCT and acute myelomonocytic leukemia; the leukemia cells coexpressed myelomonocytic antigens (HAM56, My4, My9) and cytokeratin, suggesting dual differentiation, myeloid and germ cell. Evidence for a germ cell origin of the acute leukemias in the three other patients was not obtained, although in all three the MGCT and the leukemia occurred simultaneously, supporting an etiologic relationship. Hence, these leukemias may represent another form of non-germ cell malignancy developing in germ cell tumors. All patients died of the leukemia, with a median survival of less than 2 months. This syndrome may be a useful pathologic model for the study of germ cell differentiation and hematopoietic ontogeny.

Adolescent↗
PubMed1990

Carboplatin-based chemotherapy with pharmacokinetic analysis for patients with hemodialysis-dependent renal insufficiency.

Three patients with renal insufficiency requiring hemodialysis were treated with carboplatin at 100 mg/m2 in combination with etoposide for advanced germ-cell tumor (GCT, two cases) or Adriamycin + vinblastine for a transitional-cell carcinoma of the ureter (one case). Hemodialysis was performed 24 h after the administration of carboplatin. Both patients with GCT achieved a complete response, and the patient with transitional-cell carcinoma of the ureter was inevaluable for response but his disease has not progressed. The dose of carboplatin was increased in one patient as renal function improved on therapy. In two patients, the pharmacokinetics of carboplatin were determined; the pre-dialysis half-lives, AUC, and total body clearances of free carboplatin-derived platinum were estimated to be 32 and 18.3 h, 4.93 and 6.17 mg ml-1 min, and 18.2 and 18.7 ml/min, respectively. The dialysis elimination half-lives (t1/2 beta) of 2 and 3 h, respectively, for these two patients were markedly lower than the predialysis values, indicating that carboplatin was dialyzed. In summary, carboplatin can be given to patients with severe renal insufficiency. Adequate AUCs were achieved and dialysis limited systemic exposure to free carboplatin.

Adult↗
PubMed1990

Infrequent ras oncogene point mutations in renal cell carcinoma.

The role of ras oncogenes in the pathogenesis of renal cell carcinoma is unclear. We have previously shown that insertion of a mutated ras oncogene into cultured human proximal tubular cells, the normal counterpart of renal cell carcinomas, initiates a series of transformation events which results in cells possessing a renal cancer phenotype. These data suggested a role for mutated ras genes in the initiation and maintenance of this disease. Therefore, to assess the involvement of ras genes in renal carcinogenesis, 51 primary and metastatic renal carcinomas, including three oncocytomas, were analyzed for point mutations in codons 12, 13 and 61 of the Ha-ras, Ki-ras and N-ras proto-oncogenes using polymerase-catalyzed chain reaction methodology. A mutated Ha-ras gene was found in one renal cancer metastatic to lung for an overall incidence of 2%. These data indicate that ras oncogenes, activated by point mutations, do not play a major role in the initiation, maintenance or metastases of renal carcinomas.

Adenoma↗
PubMed1990

Adjunctive surgery after chemotherapy for nonseminomatous germ cell tumors: recommendations for patient selection.

One hundred eighty-five patients who underwent surgery within 6 months of completing chemotherapy were identified from 360 patients with nonseminomatous germ cell tumors (NSGCT) treated with Memorial Hospital front-line cisplatin- or carboplatin-based combination chemotherapy protocols between 1979 and 1988. Clinical, pathologic, and radiologic features were correlated with the pathologic findings at surgery. The size of a residual retroperitoneal mass, the degree of shrinkage that occurred with chemotherapy, and the presence of teratomatous elements in pretreatment pathology specimens were each correlated with the pathologic findings of retroperitoneal resections after chemotherapy. Multivariable logistic regression analysis of those undergoing retroperitoneal resections identified the size and shrinkage of the residual mass and the prechemotherapy lactate dehydrogenase (LDH) and alphafetoprotein (AFP) levels as the best predictors of finding only necrotic debris. No factors could be found, however, that could selectively exclude patients who had residual viable malignancy or teratoma in the retroperitoneum. Of 39 patients with residual retroperitoneal masses measuring less than or equal to 1.5 cm in maximal diameter, three had residual malignancy and five had teratoma resected. No factors were identified for residual lung or mediastinal masses that could be used to select a group of patients who could safely avoid surgery. If serum markers have normalized after chemotherapy for NSGCT, resection of all residual abnormalities on imaging studies of the retroperitoneum, lungs, and mediastinum is recommended. In addition, retroperitoneal lymph node dissection (RPLND) is recommended for all patients with initial bulky metastases (greater than or equal to 3 cm in diameter) in the retroperitoneum, irrespective of the findings of postchemotherapy computed tomography (CT).

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Blood group-related antigens in human germ cell tumors.

With the use of immunohistochemical techniques, seven mouse monoclonal antibodies and the lectin from Ulex europaeus, detecting blood group antigens of the ABH and Lewis systems, have been used to define the distribution of these antigenic structures in germ cell tumors. The reagents used recognize the following blood group antigens: A, B, H, Lewisa, Lewisb, X (Lewisx), Y (Lewisy), and type I precursor antigen. Tumors from 29 patients were studied. Tumors studied consisted of pure embryonal carcinoma for eight patients, pure yolk sac tumor for two patients, embryonal carcinoma plus yolk sac tumor in one patient, and yolk sac tumor plus seminoma in one patient. Also studied were nine classic seminomas and a group of six patients with tumors classified as seminomas that exhibited atypical histological features. One patient had an anaplastic carcinoma arising from the mediastinum which could not be conclusively identified as a germ cell tumor morphologically and was analyzed separately. All embryonal carcinomas and yolk sac tumors exhibited strong positivity for type I precursor structure as detected by the K-21 monoclonal antibody. In marked contrast, there was non staining in classic seminomas but heterogeneous staining in five of six atypical seminomas. The majority of embryonal carcinomas and all yolk sac tumors studied demonstrated strong positivity for blood group antigen H. For seminoma, however, only one of the atypical cases and two of the classic cases (occasional cells) stained for H. Focal expression of the Y antigen was identified in 5 of 17 seminomas and in the majority of embryonal carcinomas and yolk sac tumors. Two yolk sac tumors and two classic seminomas expressed blood group X. The remaining blood group antigens were not expressed by seminomas while they were variably expressed by embryonal carcinoma and yolk sac tumors. These data suggest that K-21 and blood group antigen H may be distinguishing markers of nonseminomatous germ cell tumor versus seminoma. If so, it is possible that the heterogeneous expression of blood group substances in seminomas with atypical histologies is an indication of differentiation towards nonseminomatous germ cell tumor.

ABO Blood-Group System↗