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Biomedical subjects

R J Motzer

Publications and source records attributed to R J Motzer.

At least 55 records · Page 3Linked to original sources
PubMed1997

Ifosfamide- and cisplatin-containing chemotherapy as first-line salvage therapy in germ cell tumors: response and survival.

PURPOSE: To evaluate the efficacy and toxicity of ifosfamide- and cisplatin-containing chemotherapy as first-line salvage treatment for patients with germ cell tumors (GCT). PATIENTS AND METHODS: Fifty-six patients with advanced GCT resistant to one prior cisplatin-containing regimen were treated with a salvage chemotherapy regimen of ifosfamide, cisplatin, and either vinblastine or etoposide (VeIP/VIP). RESULTS: Twenty of 56 (36%) assessable patients achieved a complete response (CR). Thirteen (23%) are alive and continuously free of disease at a median follow-up time of 52 months; the median survival duration was 18 months. Among patients with a testis primary tumor site and a prior CR to first-line therapy, 65% are alive and 41% continuously disease-free, and the median survival time has not been reached. In contrast, for patients with an extragonadal primary tumor or with a testis primary tumor site and an incomplete response (IR) to first-line therapy, 31% are alive and 15% continuously free of disease, with a median survival time of 12 months (P < .03). CONCLUSION: Ifosfamide- and cisplatin-containing therapy achieves a durable CR in a minority of patients with resistant GCT as first-line therapy. Patients with a primary testis site who relapsed from a CR to first-line cisplatin therapy have a better prognosis than patients with an extragonadal primary tumor site or an IR to first-line therapy. Risk-directed clinical trials to improve response and survival in both subsets are warranted.

Adolescent↗
PubMed1997

Surgery for a post-chemotherapy residual mass in seminoma.

PURPOSE: We attempted to select patients for surgery of post-chemotherapy residual mass in advanced seminoma. MATERIALS AND METHODS: A total of 55 patients with advanced seminoma underwent surgical exploration of a mass seen on computerized tomography (CT) after chemotherapy. Residual masses were defined radiographically as smaller or larger than 3 cm. and as well defined or poorly defined. Surgery consisted of complete resection of the mass and surrounding lymph nodes or multiple biopsies at sites of disease. RESULTS: Of the 55 patients 32 (58%) had masses resected and 23 (42%) underwent multiple biopsies. Of 27 patients with a post-chemotherapy 3 cm. or larger mass on CT 8 (30%) had residual tumor (seminoma in 6 and teratoma in 2), whereas necrotic tissue was found in the other 28 patients having a mass smaller than 3 cm. Well defined masses on CT were resected in 78% of patients and poorly defined masses could be resected in only 44%. Of the 8 patients with positive histology 6 remain alive and disease-free after complete resection of a well defined, larger than 3 cm. mass containing viable tumor, and 2 with a poorly defined mass died after biopsy only of residual seminoma despite salvage therapy. Three other patients who underwent complete resection of necrotic masses subsequently had relapse at distant sites and died. Median followup was 47 months (range 5 +/- 153+ months). CONCLUSIONS: Patients with advanced seminoma who have a residual mass smaller than 3 cm. after chemotherapy do not benefit from surgery. For patients with a residual mass 3 cm. or larger we prefer surgery to define response, resect viable tumor when possible and direct further treatment.

Follow-Up Studies↗
PubMed1997

Germ cell tumors.

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Adolescent↗
PubMed1997

Adjuvant chemotherapy for testicular cancer.

Two treatment options cure nearly all patients with pathologic stage II testicular nonseminomatous germ cell tumor following a retroperitoneal lymph node dissection. These are (1) two cycles of adjuvant etoposide plus cisplatin (with or without bleomycin) chemotherapy and (2) close surveillance with chemotherapy reserved for relapse. The decision to choose one of these options is dependent on the extent of tumor involvement at surgery and patient compliance.

Antibiotics, Antineoplastic↗
PubMed1997

Paclitaxel in salvage therapy for germ cell tumors.

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) as a single agent showed antitumor activity in patients with germ cell tumors resistant to combination cisplatin-containing chemotherapy and has been included in two risk-directed first-line combination salvage programs. Patients with relapsed germ cell tumors originating from a testis primary site were treated in a phase I/II trial of conventional-dose paclitaxel (given at 175, 215, and 250 mg/m2 dose levels), ifosfamide, plus cisplatin. Ten (63%) of 16 assessable patients achieved a complete response, eight (50%) of which remain durable at a median follow-up of 16 months. The 250 mg/m2 dose of paclitaxel was chosen for the phase II trial and accrual continues. In a second trial, patients with cisplatin-resistant germ cell tumors and unfavorable prognostic features (previous incomplete response to first-line chemotherapy or an extragonadal primary site) were treated with a dose-intensive program consisting of rapid recycling of paclitaxel plus ifosfamide followed by carboplatin plus etoposide with stem cell support. The target carboplatin dose was based on the Calvert formula and escalated from an area under the concentration-time curve of 12 to 32 mg/mL min among patient cohorts. Ten (56%) of 18 assessable patients achieved a complete response, and seven (39%) remain in complete response at a median follow-up of 11 months. Hematologic toxicity was moderately severe, but no treatment-related deaths have occurred. Accrual to the trial continues, and pharmacology studies for carboplatin are being correlated with the target area under the concentration-time curve by the Calvert formula.

Antineoplastic Agents↗
PubMed1996

Management of residual mass in advanced seminoma: results and recommendations from the Memorial Sloan-Kettering Cancer Center.

PURPOSE: Guidelines for management of postchemotherapy residual mass in patients with advanced seminoma remain controversial. We sought to characterize independent prognostic factor(s) for persistence of tumor to identify patients with a high risk of residual carcinoma. PATIENTS AND METHODS: One hundred four patients with advanced seminoma were assessed. All had achieved a complete response or partial response with normal markers to induction cisplatin-based chemotherapy and had radiographs available for review. Selected prechemotherapy and postchemotherapy characteristics were compared for patients who had either germ cell tumor histology at surgery or relapsed at the assessed site (defined as site failure) versus those who had only necrosis or fibrosis found at surgery and did not relapse at the assessed site (defined as site nonfailure). RESULTS: At a median follow-up time of 47 months (range, 5 to 153), 94 patients (90%) were designated as site nonfailures and 10 (10%) as site failures. Site failure correlated only with size of the residual mass (< 3 cm or normal v > or = 3 cm; P = .0006). Two of 74 patients (3%) with residual masses less than 3 cm were considered site failures, compared with eight of 30 (27%) with residual masses > or = 3 cm. CONCLUSION: Patients with advanced seminoma who have normal radiographs or residual masses less than 3 cm after chemotherapy can be observed without further intervention. The following three options exist for patients with a residual mass > or = 3 cm: observation, radiotherapy, or surgical intervention. We prefer the latter to define response, resect viable tumor when possible, and direct further treatment.

Adolescent↗
PubMed1996

High-dose carboplatin, etoposide, and cyclophosphamide for patients with refractory germ cell tumors: treatment results and prognostic factors for survival and toxicity.

PURPOSE: The efficacy and toxicity of high-dose carboplatin, etoposide, and cyclophosphamide with autologous bone marrow transplantation (AuBMT) was investigated in a prospective trial for patients with cisplatin-refractory germ cell tumor (GCT). Prognostic factors for survival and treatment-related toxicity were identified. PATIENTS AND METHODS: Fifty-eight patients with refractory GCT were treated with high-dose carboplatin, etoposide, and cyclophosphamide plus AuBMT. Prognostic factors for toxicity and survival were examined in multivariate analyses. RESULTS: Twenty-three patients (40%) achieved a complete response and 12 (21%) are alive and free of disease at a median follow-up time of 28 months. Myelosuppression was severe and there were seven (12%) treatment-related deaths. Independently predictive factors that resulted in faster blood count recovery were the use of granulocyte colony-stimulating factor (G-CSF) for the number of days to neutrophil count recovery (P = .013) and prior treatment with cisplatin limited to six cycles or less for the number of days to platelet count recovery (P = .0012). Both were predictive for the number of days of hospitalization (P = .04 and .03, respectively). The two independently predictive variables for survival were pretreatment level of HCG; human chorionic gonadotrophin (HCG; < or = 100 times the upper limit of normal [xnl] v > 100 xnl, P = .02) and the presence of retroperitoneal metastases (yes or no, P = .04). Patients grouped by HCG < or = 100 xnl with retroperitoneal metastases, HCG < or = 100 xnl without retroperitoneal metastases, and all patients with HCG more than 100 xnl had median survival times of 14, 11, and 3 months, respectively (P = .04). CONCLUSION: High-dose carboplatin, etoposide, and cyclophosphamide is an effective therapy for patients with refractory GCT, and results in a complete response proportion of 40% and a 2-year survival rate of 31% at a median follow-up time of 28 months. This was accomplished in a group of patients with a dismal prognosis to conventional-dose therapy.

Adolescent↗
PubMed1996

Simultaneous retroperitoneal, thoracic, and cervical resection of postchemotherapy residual masses in patients with metastatic nonseminomatous germ cell tumors of the testis.

PURPOSE: We report our experience with simultaneous resection of residual masses above and below the diaphragm in patients with metastatic nomseminomatous germ cell tumor (NSGCT) of the testis. MATERIALS AND METHODS: Twenty-four patients underwent simultaneous resection of residual postchemotherapy masses in the retroperitoneum and chest, including three who also had radical neck dissection. All had been heavily pretreated with chemotherapy and five had undergone previous retroperitoneal lymph node dissections (RPLNDs). RESULTS: The combined procedure was performed with no mortality and low morbidity. The median length of the procedure was 5 hours 45 minutes, median blood loss 500 mL, and median length of hospital stay 9 days. Complications included one patient with chylous ascites and one with a prolonged air leak, both of which resolved with conservative management. Eighteen patients had similar pathologic findings in all sites: 13 with necrosis only and five with teratoma only. Six patients had discordant pathology in the abdomen and chest, including one with viable tumor in the chest only and two with viable tumor in the abdomen only. The overall actuarial 5-year survival rate for all patients was 79%. CONCLUSION: Simultaneous resection of neck, chest, and abdominal residual masses after chemotherapy for germ cell tumors is both a feasible and safe alternative to staged excision in selected patients who require surgical intervention at multiple sites and fulfills the objective of rendering patients disease-free in a single operative procedure.

Adolescent↗
PubMed1996

Adjuvant chemotherapy for stage II nonseminomatous testicular cancer: what is its role?

Two treatment options cure nearly all patients with pathological stage II testicular nonseminomatous germ cell tumor (NSGCT) following a retroperitoneal lymph node dissection (RPLND). These are (1) two cycles of adjuvant cisplatin-based chemotherapy and (2) close surveillance with chemotherapy reserved for patients who relapse. The decision to choose one of these options is dependent on the extent of tumor involvement at RPLND and patient compliance. Surveillance is the treatment of choice for compliant patients with minimal nodal involvement (<6 nodes involved, no node >2 cm, no extranodal extension; N(1), N(2a)) resected at RPLND; one third or less of these patients relapse to surveillance alone. Patients with "high volume" nodal involvement (<6 nodes involved, any node >2 cm; N(2b) or extranodal extension; N(3)) have a relapse rate of 50% to 90% to surveillance. The option of adjuvant chemotherapy in this group remains a strong consideration. A prospective trial of two cycles of etoposide plus cisplatin adjuvant chemotherapy for patients with pathological stage N(2b,3) showed that this regimen was highly effective and preferable to vinblastine-based regimens because it was better tolerated.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Expression of retinoic acid receptor beta in human renal cell carcinomas correlates with sensitivity to the antiproliferative effects of 13-cis-retinoic acid.

The differentiation and growth suppressive effects of retinoic acid are mediated through retinoic acid nuclear receptors (RARs and RXRs), which are ligand-activated transcription factors. Recent data suggest that both altered and regulated expression of RARs are linked to retinoic acid response in a cell context-dependent manner. This study examined the antiproliferative effects of 13-cis-retinoic acid (cRA) on 12 renal cancer cell lines and correlated these findings with the basal and induced expression of RAR-alpha, -beta and -gamma. Eleven of 12 renal cancers that were either resistant to or only minimally inhibited by cRA did not basally express RAR-beta as determined by Northern blot analysis. In these cells, cRA treatment did not induce RAR-beta expression. In contrast, 1 of 12 cell lines (SK-RC-06) was >90% inhibited by cRA and basally expressed RARbeta. Furthermore, RAR-beta mRNA in SK-RC-06 cells was up-regulated by cRA treatment. Amplification of cDNA using PCR and RAR-beta isoform-specific primer pairs revealed that only SK-RC-06 cells expressed the RAR-beta1 isoform. Expression of RAR-alpha transcripts was abundant in all 12 cell lines examined, whereas low levels of RAR-gamma transcripts were detectable in 6 of 10 renal cancers. Expression of RAR-alpha and RAR-gamma was not affected by cRA. These data showing that the majority of renal cancer cell lines are resistant to cRA suggest that: (a) resistance to the antiproliferative action of cRA correlates with repressed RAR-beta mRNA expression; and (b) the antiproliferative effects of cRA in renal cancer cells are mediated through RAR-beta1.

Antineoplastic Agents↗
PubMed1995

Phase III randomized trial of interleukin-2 with or without lymphokine-activated killer cells in the treatment of patients with advanced renal cell carcinoma.

BACKGROUND: Treatment with interleukin-2 (IL-2) and lymphokine-activated killer cells (LAK) resulted in responses in some patients with advanced renal cell carcinoma (RCC). However, the relative therapeutic benefit of the addition of LAK to IL-2 was unknown. METHODS: A randomized Phase III trial was conducted in patients with RCC comparing continuous intravenous infusion (CI) IL-2 alone with CI IL-2 plus LAK. Interleukin-2 was administered at 3 x 10(6) U/m2/day on days 1-5, 13-17, 21-24, and 28-31. Patients on the LAK treatment arm underwent leukapheresis on days 8-10 and LAK cell reinfusion on days 13-15. The results are reported with long-term follow-up. The published experience with IL-2 alone or with the addition of LAK was investigated in a quantitative literature survey. The response proportions were studied by schedule (high dose bolus, moderate dose, low dose) and by concomitant administration of LAK. RESULTS: Seventy-one patients were treated, 36 on the IL-2 arm and 35 on the IL-2 plus LAK arm. Four patients (6%) had major responses (two complete, two partial). The median survival of all patients was 13 months (95% confidence interval [CI], 9-18 months). There were no differences between treatment arms with regard to response (P = 0.61) and survival (P = 0.67). More patients on the LAK arm experienced pulmonary toxicity (P = 0.008). The overall weighted response proportion was 16% (95% CI, 8%-24%) for the 39 published series of 1291 patients treated with IL-2. The 95% confidence intervals for response proportion overlapped when compared by schedule and by administration of LAK. CONCLUSIONS: The dose and schedule of IL-2 used in this study resulted in a low level of antitumor activity and the addition of LAK did not improve the response rate against RCC. Given the infrequent, but reproducible, responses with IL-2 and interferon-based regimens, continued investigation of these agents is warranted as is the study of new cytokines. Alternative treatment strategies should be studied in RCC and new agents and treatment regimens that appear promising in Phase II studies must be studied in randomized trials.

Adult↗
PubMed1995

all-trans retinoic acid for treating germ cell tumors. In vitro activity and results of a phase II trial.

BACKGROUND: Germ cell tumors (GCTs) are characterized by a capacity to differentiate in vivo and in vitro. The authors' previous work highlighted the finding that retinoid-mediated GCT differentiation in vitro correlates with expression of the retinoic acid receptor-gamma. METHODS: Six human GCT cell lines were studied to determine whether their growth and differentiation were linked to the retinoic acid response pathway. The maturation and growth inhibitory responses to all-trans retinoic acid (RA) were studied as well as the expression of retinoic acid receptor-gamma (RAR-gamma). The clinical antitumor activity of RA was studied in a Phase II trial of RA in patients with chemotherapy-refractory GCTs. RESULTS: The RA response pathway was correlated with the control of growth and maturation in three of the six GCT cell lines studied. In one GCT cell line, RA induced RAR-gamma expression and terminal differentiation. In a second, there was high basal expression of RAR-gamma and poor basal proliferative potential. A third cell line showed a more mature basal phenotype than other cell lines studied and marked growth inhibition when treated with RA. Sixteen patients were treated with RA for an average of 7 weeks in the clinical trial. No complete or partial responses were noted. CONCLUSION: A Phase II clinical trial of RA failed to show significant clinical antitumor activity in patients with chemotherapy-refractory GCTs. However in vitro data suggest that the control of growth and maturation in some GCT cell lines involve the RA signaling pathway. Further studies are warranted to define the role that other retinoids with receptor selectivity or more favorable pharmacologic properties may play in the maturation or antitumor responses of GCTs.

Adolescent↗
PubMed1995

Phase II trial of topotecan in patients with cisplatin-refractory germ cell tumors.

Fifteen patients with advanced, cisplatin-refractory germ cell tumors (GCT) were treated on a phase II trial with topotecan. None of the 14 evaluable patients achieved a complete or partial response. Myelosuppression was the major toxicity. The median nadir leukocyte count was 1.75 cells/mm3, neutrophil count was 1.55 cells/mm3, hemoglobin was 8.75 gm/dl, and platelet count was 20,500 cells/mm3. Topotecan is not efficacious in the treatment of cisplatin-refractory GCT.

Adult↗
PubMed1995

Molecular and cytogenetic studies in the diagnosis of patients with poorly differentiated carcinomas of unknown primary site.

PURPOSE: A minority of patients with poorly differentiated carcinoma achieve a complete response to cisplatin therapy. Recently, specific chromosomal abnormalities have been described for several solid tumor malignancies. Molecular and cytogenetic techniques were used to study tumors of patients with midline carcinoma of unknown primary site. MATERIALS AND METHODS: Forty patients with poorly differentiated carcinoma of unknown primary site had fresh tumor samples studied by cytogenetic analysis, Southern blot analysis for 12p copy number, and fluorescence in situ hybridization (FISH) for the identification of i(12p) and chromosome 12 aneuploidy. The response to cisplatin therapy was correlated to the diagnosis provided by the genetic studies. RESULTS: In 17 (42%) patients, a diagnosis was suggested by the genetic studies. This included a germ cell tumor in 12 (30%) patients by the finding of i(12p), increased 12p copy number, or a deletion of the long arm of chromosome 12. In five patients, a specific diagnosis other than germ cell tumor was suggested by tumor karyotype. These were neuroepithelioma, lymphoma, desmoplastic small-cell tumor, melanoma, and clear-cell sarcoma. The 75% response proportion to cisplatin therapy in patients with tumors showing chromosome structural abnormalities of germ cell tumor was greater than the 18% response proportion in patients for whom no diagnosis was provided (P = .002). CONCLUSION: Molecular and cytogenetic studies are useful in establishing specific diagnoses in patients with poorly differentiated carcinomas of unknown primary site. This group of tumors is heterogeneous and is composed of germ cell tumors, melanoma, lymphoma, neuroepithelioma, and desmoplastic small-round-cell tumor in addition to some that are not yet classifiable. Response to cisplatin therapy correlates with the finding of i(12p) in tumor by either molecular or cytogenetic studies.

Adenocarcinoma↗