Biomedical subjects

M Mazumdar

Publications and source records attributed to M Mazumdar.

At least 55 records · Page 3Linked to original sources

PubMed1998

Treatment of patients with transitional-cell carcinoma of the urothelial tract with ifosfamide, paclitaxel, and cisplatin: a phase II trial.

PURPOSE: A phase II trial of ifosfamide, paclitaxel, and cisplatin (ITP) was conducted in previously untreated patients with advanced transitional-cell carcinoma (TCC) to assess its efficacy and toxicity. PATIENTS AND METHODS: Thirty patients with metastatic or unresectable TCC were treated with ifosfamide 1.5 g/m2/d for 3 days with paclitaxel 200 mg/m2 over 3 hours and cisplatin 70 mg/m2 on day 1 of each 28-day treatment cycle. Therapy was continued for a maximum of six cycles. Prophylactic hematopoietic growth factor (recombinant human granulocyte colony-stimulating factor [rhG-CSF]) was given on days 6 to 17 of each cycle. RESULTS: Twenty-three of 29 assessable patients (79%; 95% confidence interval [CI], 60% to 92%) demonstrated a major response (six complete [CR] and 17 partial [PR]) with response durations that ranged from 5 to 24+ months. Five patients with T4 bladder primary tumors had a major response, two with pathologic CR. At a median follow-up duration of 17.9 months, nine (31%) patients remain disease-free (range, 10+ to 24+). Hematologic toxicity included anemia, thrombocytopenia, and neutropenia; febrile neutropenia was observed in 17% of patients and 4% of cycles. No grade 4 nonhematologic toxicity was observed. Grade 3 nonhematologic toxicity included alopecia, allergy (3%), renal insufficiency (13%), and neuropathy (10%). Dose reductions or drug omissions were necessary for adverse events in seven (23%) patients. CONCLUSION: ITP is an active, well-tolerated regimen in previously untreated patients with TCC of the urothelial tract. Further study of this regimen in patients with both TCC and non-transitional-cell urothelial tumors is ongoing.

Adult↗

PubMed1997

Defective transport is a common mechanism of acquired methotrexate resistance in acute lymphocytic leukemia and is associated with decreased reduced folate carrier expression.

Methotrexate (MTX) transport was examined in 27 patients with untreated acute lymphocytic leukemia (ALL) and 31 patients with relapsed ALL using a previously described fluorescent MTX analog (PT430) displacement assay (Blood 80:1158, 1992). Only 13% of untreated patients were considered to have impaired MTX transport, whereas more than 70% of relapsed patients had evidence of impaired MTX transport. To further characterize the basis for this defect, Northern analyses for the reduced folate carrier (RFC) were performed on the RNA available from the leukemic blasts of 24 patients in whom MTX transport had been measured. Six of nine samples with impaired MTX transport had decreased RFC expression (one had no detectable RFC expression), while three had no decrease in RFC expression. None of 15 samples with normal MTX transport had decreased RFC expression. A reverse-transcriptase polymerase chain reaction (RT-PCR) assay was developed to quantitate RFC mRNA expression more accurately. Decreased RFC expression was demonstrated in six of the nine samples with impaired MTX transport, confirming the results obtained by Northern blot. These data indicate decreased RFC expression associated with impaired MTX transport is observed in relapsed ALL following treatment with MTX-containing therapy.

Adolescent↗

PubMed1997

A phase II study of 13-cis-retinoic acid in patients with advanced renal cell carcinoma.

The aim of this study was to determine the antitumor activity of 13-cis-retinoic acid as a single agent in patients with advanced renal cell carcinoma. Eligible patients had advanced renal cell carcinoma with bi-dimensionally measurable disease, a Karnofsky performance status of at least 70, life expectancy of greater than three months, no evidence of brain metastases, and treatment with no more than one chemotherapy regimen. Patients were treated with one mg/kg/day of 13-cis-retinoic acid orally. Twenty-six patients were enrolled in this study and 25 were evaluable for response and toxicity. Of the twenty-five evaluable patients, no major responses were achieved. Toxicity was mild, with no patient requiring a dose reduction. At the dose administered in this trial, 13-cis-retinoic acid is inactive as a single agent in renal cell carcinoma.

Adult↗

PubMed1997

Phase II trial of docetaxel in patients with advanced or metastatic transitional-cell carcinoma.

PURPOSE: A phase II trial of docetaxel was conducted to assess its efficacy and toxicity in patients with advanced transitional-cell carcinoma (TCC) who had failed to respond to prior cisplatin-based therapy. PATIENTS AND METHODS: Thirty assessable patients who had failed to respond to or relapsed after one prior cisplatin-containing regimen were treated with docetaxel 100 mg/m2 over 1 hour, every 21 days. All patients were premedicated with dexamethasone and diphenhydramine to reduce allergic reactions. Reductions of subsequent doses were made for severe hematologic toxicity. Prophylactic hematopoietic growth factors were not used. RESULTS: Four of 30 patients (13.3%; 95% confidence interval [CI], 3.8% to 30.7%) demonstrated a partial response (PR), with durations of response ranging from 3 to 8 months. The estimated median survival duration for all patients is 9 months (95% CI, 6 to 12 months) with a median follow-up time of 14 months (range, 1 to 27). Hematologic toxicity included anemia, thrombocytopenia, neutropenia, and febrile neutropenia. Nonhematologic toxicity included alopecia and mucositis. Fluid retention was not observed and cutaneous toxicity was mild and infrequent. Dose reductions were necessary for adverse events in 18 patients (60%). CONCLUSION: Docetaxel is an active single agent in previously treated patients with TCC of the urothelial tract. Therapy was well tolerated in this patient population but myelosuppression was frequent. Further study in previously untreated patients, both alone and in combination, is warranted.

Adult↗

PubMed1997

Phase II randomized trial of gallium nitrate plus fluorouracil versus methotrexate, vinblastine, doxorubicin, and cisplatin in patients with advanced transitional-cell carcinoma.

PURPOSE: A phase II randomized trial of gallium nitrate/fluorouracil (5-FU) versus dose-intense methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) was performed in poor-risk patients with advanced urothelial tract tumors. The efficacy and toxicity of these regimens were compared. Assessment of dose-intense M-VAC as salvage treatment in patients who failed to respond to the gallium nitrate/5-FU regimen was also performed. PATIENTS AND METHODS: Thirty-four patients who had not received prior systemic chemotherapy were randomized to either arm of the study. All patients had one or more clinical features predicting a low likelihood of durable complete response to standard chemotherapy, ie, weight loss, visceral metastases, and low performance status. Gallium nitrate and 5-FU were each administered by continuous 5-day infusions every 28 days. M-VAC was recycled every 21 days, with prophylactic recombinant human granulocyte colony-stimulating factor (rh-G-CSF). RESULTS: Two of 17 patients (12%; 95% confidence interval [CI], 1.4% to 36.4%) had a major response to gallium nitrate/5-FU. Sixteen of 17 patients treated with M-VAC (94%; 95% CI, 71.3% to 99.8%) demonstrated a major response. Five of 12 patients who failed to respond to the gallium nitrate/5-FU combination responded to M-VAC as second-line therapy (42%; 95% CI, 15.2% to 72.3%). Median survival for the gallium nitrate and 5-FU arm was 19 versus 17 months for the M-VAC arm, with a median follow-up duration of 35 months (range, 2 to 51) for all patients. Dose-intense M-VAC was associated with a greater incidence of neutropenia and thrombocytopenia. CONCLUSION: Dose-intense M-VAC is superior to gallium nitrate/5-FU in poor-risk patients (P < .0001). Despite the overall high response rate, the median survival for patients with M-VAC remained unsatisfactory. Similar survival distributions were observed for patients who received investigational therapy followed by cisplatin-based therapy and patients treated with initial cisplatin-based therapy.

Adult↗

PubMed1997

High-dose carboplatin, etoposide, and cyclophosphamide with autologous bone marrow transplantation in first-line therapy for patients with poor-risk germ cell tumors.

PURPOSE: A treatment program that included high-dose carboplatin, etoposide, and cyclophosphamide (CEC) followed by autologous bone marrow transplantation (AuBMT) was investigated as first-line therapy in patients with poor-risk germ cell tumors (GCTs). PATIENTS AND METHODS: Previously untreated GCT patients with poor-risk features were treated with etoposide, ifosfamide, and cisplatin (VIP) with or without high-dose CEC plus AuBMT. Patients qualified for a change to high-dose CEC if a prolonged clearance of elevated serum tumor markers was observed after two cycles of the cisplatin-containing regimen. RESULTS: Sixteen patients were treated with VIP alone and 14 with VIP and high-dose CEC. Seventeen patients (57%) achieved a complete response. Twenty are alive (67%) and 15 (50%) are free of disease at a median follow-up time of 30 months. For 23 cycles of high-dose CEC, the median time from AuBMT to a granulocyte count > or = 0.5/microL was 11 days (range, 0 to 14) and to a platelet count 50,000/microL, 19 days (range, 14 to 34). The survival of 58 patients treated in two of our center's programs that incorporated high-dose chemotherapy (high-dose carboplatin plus etoposide [CE] and CEC) was compared with our prior experience with conventional-dose cisplatin chemotherapy alone in poor-risk GCT. Patients treated with marker-dependent, early-intervention high-dose chemotherapy experienced longer survival (P = .001). CONCLUSION: In this setting, high-dose CEC was well tolerated, cumulative toxicity was lacking, and the recovery of blood counts after AuBMT was rapid. A randomized trial has been initiated to investigate further the role of high-dose CEC in first-line therapy for patients with poor-risk GCT.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1997

Long-term follow-up of patients with good-risk germ cell tumors treated with etoposide and cisplatin.

PURPOSE: To assess the durability of response and overall survival for patients with good-risk metastatic germ cell tumors (GCT) treated with four cycles of etoposide and cisplatin (EP). PATIENTS AND METHODS: Two hundred fourteen patients treated with EP on two consecutive randomized trials for good-risk metastatic GCT were the subject of this retrospective study. The response to therapy, relapse and survival status, and results of salvage therapy are reported. RESULTS: One hundred ninety-five patients (91%) achieved a complete response (CR). This included 182 patients (85%) who achieved a CR to chemotherapy alone and 13 patients (6%) who achieved a CR to chemotherapy plus surgical resection of viable GCT. Seventeen patients (9%) have relapsed from CR. The median time to relapse was 10 months, and the longest duration from treatment to relapse was 36 months in a patient who received three of four planned courses of therapy. Eight patients who either achieved an incomplete response (IR) or relapsed were rendered continuously disease-free by salvage therapy and are alive. One hundred eighty-three patients (86%) are alive at a median follow-up of 7.6 years. CONCLUSION: Four cycles of EP constitute effective therapy and can be offered to patients with good-risk GCT. In patients with intermediate- and poor-risk GCT, clinical trials remain a priority to identify more effective treatment.

Adolescent↗

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

Bicalutamide for advanced prostate cancer: the natural versus treated history of disease.

PURPOSE: To determine the therapeutic effects of bicalutamide 200 mg in patients with prostate cancers of different hormone sensitivities. METHODS: Patients with progressive prostate cancer were treated with bicalutamide 200 mg daily. Before treatment, patients' tumors were classified on the basis of prior hormone exposure and by serum testosterone levels into androgen-dependent and androgen-independent groups. Prior exposure to flutamide and response to flutamide withdrawal was also considered. Outcomes were reported independently on the basis of posttherapy changes in prostate-specific antigen (PSA), measurable disease, and radionuclide bone scans. RESULTS: Outcomes varied by prior hormone exposure as a higher proportion of patients with progression of androgen-dependent tumors showed posttherapy PSA decreases of more than 50% or more than 80%, measurable disease regression, and improvement on radionuclide bone scans than did patients with androgen-independent progression. Within the category of androgen-independent progression, clinical benefit was observed in patients who had previously progressed on flutamide, independent of the response to flutamide withdrawal. Patients who had progressed on a gonadotropin-releasing hormone (GnRH) analog alone had a low response proportion, whereas those who progressed after two or more hormone therapies did not respond. Overall, the drug was well tolerated. After progression on bicalutamide monotherapy, one third of patients with androgen-dependent progression responded to medical castration with a GnRH analog. CONCLUSION: Classifying patient tumors on the basis of prior hormone exposure permits a more precise estimate of the potential benefit of a specific hormone therapy for the individual patient. The precision is further increased by reporting the effects of a drug on each parameter of disease independently. The difference in outcomes for patients with androgen-independent progression suggests that the specific hormone therapy administered and the response to that therapy can influence the biology of the relapsing tumor and the sensitivity to subsequent therapies. The sensitivity to bicalutamide after progression on flutamide deserves further study.

Aged↗

PubMed1996

Clinical trials in relapsed prostate cancer: defining the target.

A re-examination of the methods of developing new treatments for patients with prostate cancer whose disease has progressed during hormone therapy is necessitated by the following: 1) the impact of prostate-specific antigen (PSA) testing on patient selection, 2) the increasing number of studies using noncytotoxic approaches, and 3) the lack of validated methods to report outcomes. PSA monitoring after primary therapy has increased the number of patients referred for therapy with a rising value in this marker or an asymptomatic change in a radionuclide bone scan as the only manifestation(s) of relapse. The development of drugs for this population of patients presents a unique challenge because the classical criterion used to assess efficacy in the phase II setting, i.e., the presence of objective changes in measurable disease sites, frequently does not apply. Since no approach has been proven to prolong survival, the highest priority must be placed on developing new therapies. Standardizing the methods for evaluating treatments is also essential so that promising strategies are pursued and inactive therapies are not developed further.

Biomarkers, Tumor↗

PubMed1996

In vitro motility from recombinant dynein heavy chain.

The dyneins are a class of motor protein involved in ciliary and flagellar motility, organelle transport, and chromosome segregation. Because of their large size and subunit complexity, relatively little is known about their mechanisms of force production and regulation. We report here on the expression and analysis of the entire rat cytoplasmic dynein heavy chain (Mr 532,000). Full-length cDNAs were constructed from a series of partial clones and tagged at the C terminus with either a FLAG-epitope tag or a His6-tag. The recombinant polypeptides were expressed either in insect cells by baculovirus infection or in COS-7 cells by transient transfection. The recombinant protein was mostly soluble and showed good microtubule binding. It exhibited a broad sedimentation profile, indicative of the formation of dimers as well as higher order multimers. Good microtubule gliding motility activity was observed in assays of heavy chain expressed in either insect or COS-7 cells. Average microtubule gliding velocities of 1.2-1.8 microm/sec were observed, comparable with the rates determined for calf brain cytoplasmic dynein. These results represent the first indication that recombinant heavy chain alone is capable of force production, and should lead to rapid progress in defining the dynein motor domain.

Amino Acid Sequence↗

PubMed1996

Acid phosphatase: defining a role in androgen-independent prostate cancer.

OBJECTIVES: In multivariable analysis, post-therapy change in prostate-specific antigen (PSA) was shown to be the most significant factor predictive of survival in patients with androgen-independent prostate cancer. To refine the model, we studied the patterns of change in acid phosphatase, alkaline phosphatase, and lactate dehydrogenase after treatment. METHODS: One hundred seven patients with androgen-independent prostate cancer treated on seven different protocols in Memorial Sloan-Kettering Cancer Center were evaluated. For tumor-specific (acid phosphatase and PSA) and nontumor-specific (alkaline phosphatase and lactate dehydrogenase) enzymes, a minimum 50% or 80% decrease from baseline documented on three separate occasions a minimum of 6 weeks apart was required to categorize a patient as having a decline. RESULTS: Nineteen patients (18%) had either a 50% decline in acid phosphatase or PSA, of whom 13 (68%) had a decline of both markers. Six (32%) patients showed discordance between the two parameters. Declines in PSA level typically preceded declines in acid phosphatase levels. The median survival of patients showing declines in both markers exceeded that of patients showing declines in PSA alone by 1 year. Although baseline measurements of alkaline phosphatase or lactate dehydrogenase did add additional prognostic information, post-therapy changes did not. CONCLUSIONS: Post-therapy declines in PSA and acid phosphatase represent reproducible endpoints for clinical trials in androgen-independent disease. The requirement of a repeated and parallel decline in both markers may improve the results observed by monitoring declines in PSA alone. Monitoring the two parameters may allow the development of models that can be used as surrogate endpoints for response and survival in a disease in which reproducible measurements of response are lacking.

Acid Phosphatase↗

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↗

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

Amplification of the dihydrofolate reductase gene is a mechanism of acquired resistance to methotrexate in patients with acute lymphoblastic leukemia and is correlated with p53 gene mutations.

Although dihydrofolate reductase (DHFR) gene amplification is a common mechanism of resistance to methotrexate (MTX) in tumor cell lines, with the exception of a few case reports, the incidence of this phenomenon as a mechanism of MTX resistance in the clinic has not been reported. We studied 38 untreated patients and 29 patients in relapse with acute lymphoblastic leukemia (ALL) for gene amplification and p53 gene mutations. Three patients were studied both at diagnosis and at each of two relapses after treatment with MTX. Nine of 29 relapsed patients (31%) had low-level DHFR gene amplification (two to four gene copies) associated with increased levels of DHFR mRNA and enzyme activity. Of significance was a correlation of gene amplification with p53 mutations in seven of nine relapsed patients (P < .001). Low-level DHFR gene amplification may be an important cause of MTX resistance in ALL and strengthens the concept that mutations in the p53 gene may lead to gene amplification as a consequence of defective cell cycle control.

Adolescent↗

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↗

PubMed1995

Etoposide and cisplatin adjuvant therapy for patients with pathologic stage II germ cell tumors.

PURPOSE: Two options cure nearly all patients with pathologic stage II nonseminomatous germ cell tumors (NSGCTs): two cycles of adjuvant chemotherapy with cisplatin, vinblastine, and bleomycin (PVB) or cisplatin, vinblastine, bleomycin, cyclophosphamide, and dactinomycin (VAB-6); or close observation with full treatment at relapse. Two cycles of etoposide plus cisplatin (EP) were given to selected patients with pathologic stage II NSGCT and high-volume nodal metastases. PATIENTS AND METHODS: All patients had pathologic stage II NSGCT with one or more of the following features found at retroperitoneal lymph node dissection (RPLND), suggesting a greater than 50% likelihood of relapse after observation alone: (1) any lymph node involved by tumor greater than 2 cm (stage N2b); (2) > or = six nodes involved with tumor (stage N2b); and (3) extranodal extension (stage N3). Two cycles of therapy were given at 21-day intervals; each cycle consisted of etoposide 100 mg/m2 plus cisplatin 20 mg/m2 per day given on days 1 to 5. RESULTS: Fifty patients were treated with two cycles of EP. Treatment was well tolerated; five patients (10%) were admitted for nadir fever and none had grade II or greater neurologic, renal, or pulmonary toxicity. All 50 patients are alive and relapse-free at a median follow-up time of 35 months (range, 12 to 72). The follow-up duration has been > or = 2 years for 42 patients. CONCLUSION: A treatment program that consists of two cycles of EP is effective in preventing relapses in patients with completely resected pathologic stage N2b and N3 NSGCT. The likelihood of relapse without adjuvant cisplatin-containing chemotherapy in this group has been shown to be greater than 50%. As has been demonstrated in patients with disseminated germ cell tumor (GCT), EP can be considered a therapeutic option in the adjuvant setting for completely resected N2b and N3 NSGCT.

Adolescent↗