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C N Sternberg

Publications and source records attributed to C N Sternberg.

At least 55 records · Page 3Linked to original sources
PubMed1993

Neoadjuvant M-VAC (methotrexate, vinblastine, doxorubicin, and cisplatin) for infiltrating transitional cell carcinoma of the bladder.

BACKGROUND: Based on the excellent results with combination chemotherapy such as M-VAC (methotrexate, vinblastine, doxorubicin, and cisplatin) in patients with advanced disease, neoadjuvant chemotherapy has been advocated to improve survival and in some cases to permit bladder conservation. METHODS: A Phase II study of neoadjuvant M-VAC chemotherapy was performed in patients with T2-T4N0M0 bladder tumors. After clinical staging, three cycles of M-VAC were given. After patients underwent postchemotherapy clinical restaging, pathologic restaging (partial or radical cystectomy) was planned. RESULTS: Forty-six patients are evaluable. A clinical response was attained in 78%. Six patients (13%) had stable disease, and four (9%) had progression. After chemotherapy, 17 patients underwent radical cystectomy, none of whom were pTO. In this group, 10 of the 17 (59%) are alive at a median follow-up of 37+ months (range, 8-62+ months). Eleven patients had a partial cystectomy; 7 of the 11 (64%) are alive, 6 (55%) with a preserved bladder. Eighteen patients had clinical restaging only, and did not have pathologic staging. Median follow-up for this group is 36+ months (11-65+ months). Twenty-one of the 29 (72%) patients managed with conservative surgery or transurethral resection of the bladder alone are alive with a functional bladder. Median survival for all patients has not yet been reached. Two-year survival is 82%, and 3-year survival is 70%. CONCLUSIONS: The current study is of interest in terms of bladder conservation. Assessment of the true success of any bladder-preserving treatment will require longer follow-up.

Aged↗
PubMed1993

Adjuvant chemotherapy following radical cystectomy.

The optimal management of invasive bladder cancer remains controversial. Combination chemotherapy regimens have been increasingly advocated in association with definitive local therapy in an attempt at eradicating micrometastases and reducing the risk of recurrence. Chemotherapy used after radical cystectomy is referred to as "adjuvant" therapy. The term adjuvant is occasionally used for chemotherapy following an aggressive transurethral resection (TUR). Decisions concerning individual patients must be made after careful examination of the histologic specimen and cognizance of the known relapse rates per pathologic stage. No randomized trial has reported results on patients with pT 2 and pT 3a tumors. Studies have not clearly proven any advantage for adjuvant therapy based on muscle infiltration alone (pT 2, pT 3a). For patients with minimal extravesical extension (pT 3b), additional therapy may be useful. For patients with nodal metastases (pN+) and direct extension into the adjacent viscera (pT 4), the data suggest a trend toward improved survival. These patients may benefit from adjuvant chemotherapy. The difficulties of clinical trials following cystectomy, conducted in an elderly patient population, done over a long period, with changing standards of effective chemotherapeutic regimens are described. Adjuvant therapy following cystectomy or an aggressive TUR remains investigational and its benefit has not yet been proven. Patients should be entered into well-designed and carefully conducted clinical trials to evaluate the role of chemotherapy in invasive bladder cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Treatment of brain metastases from bladder cancer.

The records of 28 patients with transitional cell cancer who had brain metastases were retrospectively reviewed. Data from 19 patients were considered suitable for analysis and were included in this study. One patient was treated with surgery alone, 10 with radiation alone and 7 with radiation and surgery, while 1 received no treatment. Mean and median survival times, respectively, were 57 and 42 months from the initial diagnosis, and 11 and 4 months from diagnosis of central nervous system metastases. Patients treated with surgery and radiation demonstrated a mean survival time of 19 months compared to 6 months for patients treated with radiation alone (p = 0.03). There were 2 long-term survivors in the combined modality group at 50 and at 12 months. Enthusiasm for combined modality treatment should be tempered by the fact that selection bias favored the combined modality group; 13 patients with single lesions demonstrated a mean survival of 14 months compared to 3 months for 6 patients with multiple lesions (p = 0.009) and only patients with solitary lesions underwent surgical resection. Brain metastases have an ominous prognosis in patients with bladder cancer primaries. Considering the sum of the retrospective and prospective reports, we recommend that patients with solitary brain lesions and good performance status be aggressively managed with surgical resection and postoperative radiation therapy.

Adult↗
PubMed1993

Carboplatin and 5-fluorouracil in poor performance status patients with advanced urothelial cancer.

BACKGROUND: In view of the difficulties in administering aggressive treatment to elderly patients, frequently with concomitant medical problems, a treatment program with the combination of carboplatin and 5-FU for advanced urothelial tumors was designed. The aim was to maintain an efficacious therapeutic schedule while minimizing toxicity. PATIENTS AND METHODS: Twenty-three patients with advanced bidimensionally measurable urothelial carcinoma were given carboplatin 100 mg/m2 and 5-fluorouracil 500 mg/m2 days 1-3 which was escalated to carboplatin 125 mg/m2 and 5-fluorouracil 625 mg/m2. 5 patients were > 70 years, the ECOG performance status was 2-3 in 10 patients (43%), and the creatinine was > 2.0 mg/dl in 3 patients (13%). Five patients (22%) had pre-existing cardiac disease, and 1 had hepatopathy. Nine patients (39%) had prior cisplatin. RESULTS: Ten patients remained at level 1, and 12 others had the dosage escalated to level 2. Twenty-one patients are evaluable for response. Response was observed in 5 of 21 (24%) evaluable patients (95% confidence limits 15%-33%), only at dose level 2. There was 1 CR (5%) and 4 PR (19%). There were no responses in patients who had prior DDP versus 5 of 13 (38%) responses in patients who had not had prior DDP. The median time to response was 2 months. The median duration of response was 8 months. At level 2 myelotoxicity was significant, and led to a return to level 1 in 2 patients. Nine of 12 patients (75%) treated at level 2 had grade 3 leukopenia, and 1 patient had nadir sepsis. 4 patients (33%) had grade 4 thrombocytopenia. CONCLUSIONS: Moderate activity was shown with this regimen in untreated patients at level 2. This regimen presents a feasible outpatient alternative for patients who are unable to undergo more aggressive chemotherapy.

Aged↗
PubMed1993

Escalated M-VAC chemotherapy and recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) in patients with advanced urothelial tract tumors.

BACKGROUND: The M-VAC regimen (methotrexate, vinblastine, adriamycin, and cisplatin) has significant antitumor activity in patients with advanced urothelial tract cancer. Growth factors may provide the possibility of treating patients with higher doses of chemotherapy, for longer periods, with less morbidity, and improved results. A trial of an escalated dosage of M-VAC with recombinant GM-CSF (rhGM-CSF) was initiated. PATIENTS AND METHODS: 23 patients were treated with an escalated dose of M-VAC every 2 weeks plus rhGM-CSF 250 micrograms/m2 s.c. days 4-10. Dose level I (n = 13) was 1.65 times the dose of standard M-VAC. Adriamycin and cisplatin were given at 2.5 times the dose of standard M-VAC. Dose level II (n = 10) was a relative dose intensity of 1.95. Adriamycin and cisplatin were both given at 2.9 times the dose. CONCLUSIONS: The response rate was 70% (95% CI 60%-80%). Seven patients (30%) had CR, and 9 (39%) had a PR. Five (22%) patients had stable disease and 2 (9%) had progression. Of the CR patients, 3 had the CR confirmed pathologically (CRp). Response occurred in 11 patients treated at dose level I and 5 at dose level II. Toxicity was primarily hematologic. Dose level II was too toxic due to thrombocytopenia. Non-hematologic toxicity was minimal. The value of this schedule (dose level I) compared to standard M-VAC will be further evaluated in a randomized trial to be initiated by the Genitourinary Group of the EORTC.

Aged↗
PubMed1993

Role of primary chemotherapy in stage I and low-volume stage II nonseminomatous germ-cell testis tumors.

After many years of debate, it has been established that radiation, retroperitoneal lymphadenectomy, and close surveillance all lead to excellent survival rates in patients with stage I nonseminomatous germ-cell tumors. Retroperitoneal lymphadenectomy may be particularly appropriate for patients seen in referral centers to which patients cannot easily return for regular follow-up. A growing understanding of prognostic factors has provided the stimulus for a third option, adjuvant chemotherapy after orchiectomy in high-risk patients. Quality of life issues must ultimately be considered when evaluating treatment options. For small-volume stage II disease, retroperitoneal lymphadenectomy is the current standard in the United States. Adjuvant chemotherapy may be given, but observation with chemotherapy for relapse is also feasible. In Europe, initial chemotherapy with later lymphadenectomy if necessary is the usual approach.

Humans↗
PubMed1992

Recombinant tumor necrosis factor for superficial bladder tumors.

Twenty patients with histologically documented superficial bladder cancer (Ta, T1, Tis) were treated with intravesical administration of TNF 400-1800 micrograms. Of 18 patients with a marker lesion, 2 obtained a complete response for 8+ and 18 months. Two had a partial response and were given other intravesical therapies after 5 and 7 months. No or minimal systemic absorption of TNF was observed and documented in 4 of 20 patients by pharmacokinetic studies, and no patients developed antibodies to intravesically administered TNF. TNF was well tolerated in doses up to 1800 micrograms. No systemic or local side effects were observed. Modest activity was attained with intravesical TNF, even in pretreated patients.

Administration, Intravesical↗
PubMed1991

Continuous infusion gallium nitrate for patients with advanced refractory urothelial tract tumors.

A Phase I-II trial of gallium nitrate was conducted in 40 patients with bidimensionally measurable urothelial tract tumors who had failed to respond to combination chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin. Partial responses were observed in 4 of 23 patients (17.4%) who received 350 mg/m2/d or more for 5 days by continuous intravenous infusion. In two additional patients who received 350 mg/m2/d or more, a minor response and a mixed response were observed. The median duration of response was 4 months (range, 2 to 8 months). A dose-response relationship was suggested because no responses were observed in 17 patients who received less than 350 mg/m2/d. Myelosuppression was minimal. The dose-limiting toxic reaction was a reversible optic neuropathy that occurred in 3 of 11 patients who received 400 mg/m2/d. Further evaluation of infusional gallium nitrate is warranted in patients with urothelial tract malignant tumors.

Adult↗
PubMed1991

Transurethral resection of the prostate and metastatic prostate cancer.

Demonstration of malignant cells in blood specimens collected during transurethral resection of the prostate (TURP) has implicated TURP in the dissemination of prostatic cancer. Of 153 patients who underwent radiation therapy for prostate cancer between January 1977 and June 1990 and were retrospectively analyzed, 93 were evaluable. Fifty-nine patients required TURP before radiation therapy for prostatic obstruction (BPH and/or cancer); the remaining 34 patients underwent radiation therapy after fine-needle aspiration biopsy. No statistically significant difference in failure rate could be detected between these groups, with a failure rate of 47% (28 of 59 patients) at a median follow-up time of 49 months (range, 8 to 146 months) in the TURP group versus a failure rate of 47% (16 of 34 patients) at a median follow-up time of 50 months (range, 3 to 122 months) in the group who underwent biopsy only (Fisher's exact test, P = 0.23). Within the confines of this retrospective study, it appeared that TURP did not enhance the development of metastatic disease.

Adenocarcinoma↗
PubMed1991

Prognostic factors for survival of patients with advanced urothelial tumors treated with methotrexate, vinblastine, doxorubicin, and cisplatin chemotherapy.

Between February 1983 and February 1986, 132 patients with advanced urothelial tract tumors were treated with methotrexate, vinblastine, Adriamycin (doxorubicin), and cisplatin (M-VAC) chemotherapy. Analysis of prognostic factors for survival of the first 92 patients was undertaken using the Cox proportional hazards model. Normal alkaline phosphatase and high Karnofsky performance status (KPS) were predominant for long survival. Patients 60 years or older at initiation of therapy were likely to survive longer than younger patients, perhaps indicating physician selectivity of older patients for this therapy, and those with initial hemoglobin in the normal range were also likely to survive longer. The additional 40 patients' data were used to validate the model. Clinical implications of the prognostic factors are discussed.

Adult↗
PubMed1991

[Chemotherapy in the treatment of advanced urothelial tumors].

Progress has been made in the management of patients with advanced metastatic and muscle-invasive urothelial tract tumors. Combination chemotherapy has proved effective, and, in those who attain complete remission it prolongs survival. Chemotherapy alone or combined with radiotherapy and TURB may now make less aggressive surgery and bladder conservation possible in selected patients. Improvements in perioperative care, coupled with surgical, radiotherapeutic and diagnostic achievements, have led to substantial progress. Recombinant DNA technology has led to the availability of sufficient quantities of hematopoietic factors, which are now available for clinical trials. Today, CSFs can complement therapy and ameliorate the myelosuppression and mucositis associated with chemotherapy, permitting safer administration of therapy and increased dose intensity of treatment programs. Investigations of the biology of bladder cancer aimed at defining the malignant and metastatic potential of an individual tumor are very promising. Immunohistochemistry of cell surface antigens, such as blood group antigens, monoclonal antibody technology, and assessment of the chromosomal complement or DNA content will have increasing importance for this aim in the future. Future trials will need to consider the biology of bladder cancer and more sophisticated prognostic variables than performance status. Mixed-histology tumors are probably less responsive. Why certain tumors metastasize and others remain restricted to the bladder or nodes is still a matter of conjecture. Hopefully, future studies will throw some light on these still-unexplained areas.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Methotrexate, vinblastine, doxorubicin, and cisplatin for advanced transitional cell carcinoma of the urothelium. Efficacy and patterns of response and relapse.

Of 133 patients with advanced urothelial tract cancer given methotrexate (MTX), vinblastine (VBL), Adriamycin (ADR) (doxorubicin; Adria Laboratories, Columbus, OH), and cisplatin (DDP) (M-VAC regimen), significant tumor regression occurred in 72% +/- 8% of 121 with transitional cell carcinoma (TCC) evaluable for response. Complete remission (CR) was achieved in 36% +/- 9% of patients, of whom 11% required the addition of surgical resection of residual disease. Although 68% of CR patients have relapsed, CR median survival will exceed 38 months compared with 11 months for partial (36%) and minor (6%) responders, and 8 months for nonresponders: 2-year and 3-year survivals were 68% and 55%, respectively, versus 0% to 7% for the remaining patients. Sixteen percent of responders developed brain lesions, half of whom had no systemic relapse at the time of progression. Three patients with non-TCC histologies did not respond. In 32 patients who had pathologic restaging, the clinical (T) understaging (T less than pathologic [P] restaging) error was 35%. Although all metastatic sites showed evidence of tumor regression, CR was noted more frequently in lung, in intraabdominal lymph nodes and masses, and in bone (24% to 35%); the rate for hepatic lesions was 15%. There were 52% of 21 N3-4M0 patients who achieved CR versus 33% of 100 with N0-+M+ lesions. Toxicity was significant with 4 (3%) drug-related deaths, 25% incidence of nadir sepsis, 58% greater than or equal to 3+ myelosuppression, and 49% with mucositis. Responsiveness of metastasis in various sites, patterns of relapse, and the usefulness of the new CR response criteria are reported, as is the current status of cisplatin and methotrexate combination regimens.

Adult↗
PubMed1988

M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) for advanced transitional cell carcinoma of the urothelium.

Of 92 patients who received methotrexate, vinblastine, doxorubicin and cisplatin complete and partial remissions were observed in 69 +/- 10 per cent of 83 adequately treated measurable and evaluable patients with advanced stages (N+M0 and N0M+) transitional cell urothelial cancer. Complete remission was achieved in 37 +/- 10 per cent of the patients clinically, pathologically and after surgical resection of residual disease. With 17 of 31 complete responders (55 per cent) surviving for 26+ to 49+ months, the estimated probability of survival at 2 and 3 years was 71 and 55 per cent, respectively. Partial remission occurred in 31 +/- 10 per cent of the patients, while 8 per cent had a minor response and 23 per cent had progression with median survivals of 11, 11 and 7 months, respectively. Whereas all metastatic sites responded, including the bone and liver, complete tumor regression was observed more frequently with nodal, pulmonary and local-regional lesions. Brain metastases occurred within 6 to 42 months in 18 per cent of the responders, half of whom never had systemic relapse. Of the remaining 9 patients 2 with nontransitional cell histological tumors did not respond, 5 (5 per cent) were inadequately treated and 2 were excluded from response data because of inevaluable disease parameters but they were free of disease at 16+ and 31+ months. Toxicity was significant, with 20 per cent of the patients experiencing nadir sepsis, 4 per cent a drug-related death, 31 per cent +1 renal toxicity and 41 per cent +1 mucositis. The applications and advantages of the newly proposed international response criteria for bladder cancer are discussed in reference to 25 patients who underwent surgical re-staging, indicating that the disease was understaged clinically in 24 per cent (T less than P), as well as in reference to attainment of true (pathological) complete remission and to other urothelial tract trials. While this therapy seems to have limited antitumor activity against nontransitional cell histological cancer, stage Tis disease and later development of de novo lesions, the regimen is efficacious in selected patients with advanced urothelial tract transitional cell carcinoma.

Adult↗