Chemotherapy and bladder cancer.
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Antineoplastic Combined Chemotherapy Protocols↗
Biomedical subjects
M B Garnick
Publications and source records attributed to M B Garnick.
Clinical promise of new hematopoietic growth factors: M-CSF, IL-3, IL-6.
Hematopoietic growth factors are reaching maturity in clinical trials. There is a wide spectrum of disorders of bone marrow dysfunction that can be effectively treated by currently available hematopoietic growth factors. Newer growth factors are entering clinical trials. rhM-CSF has a variety of biological activities. It may be useful in hematology/oncology and infectious disease settings. Recombinant human interleukin-3 (rhIL-3) has undergone extensive trials in nonhuman primates that suggest that this hematopoietin is a potent stimulus of bone marrow function following chemotherapy and may be synergistic with other growth factors, such as rhGM-CSF. Other pleotrophic hematopoietic growth factors, such as interleukin-6, are currently being developed and may exert a wide spectrum of activities in disease states.
Acute Disease↗
Case 48-1987: pulmonary mass of 3 1/2 years' duration.
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Adult↗
Metastatic testicular teratoma invading the inferior vena cava.
We report a case of a teratoma thrombus within the inferior vena cava subsequent to chemotherapy for embryonal carcinoma of the testis. A review of the literature indicates that intracaval metastases occur in approximately 1 per cent of the patients with bulky retroperitoneal disease. Seminoma and embryonal carcinoma have been identified previously within the inferior vena cava, and teratoma is now added to that list. The potential lethality of teratoma owing to local growth alone is underscored by its intracaval presence in this case. We recommend close inspection of the inferior vena cava at operation for bulky disease to exclude an intracaval thrombus, as well as complete excision of all residual masses following chemotherapy for testis cancer.
Adult↗
Stage II nonseminomatous germ cell tumors of the testis: an analysis of treatment options in patients with low volume retroperitoneal disease.
The management of patients with nonseminomatous germ cell tumors of the testis and low volume retroperitoneal disease remains controversial. We analyzed the treatment modalities of 56 patients divided into 3 groups: group I--18 clinical stage I cancer patients who had pathological stage II disease after retroperitoneal lymph node dissection, group II--31 patients with abdominopelvic computerized tomography abnormalities of 5 cm. or less with or without positive biological markers and group III--7 patients with persistently positive biological markers after orchiectomy with normal abdominopelvic computerized tomography scans. In group I 4 of 18 patients received chemotherapy after retroperitoneal lymph node dissection. Two patients met criteria for post-dissection chemotherapy, but they did not receive it and subsequently had relapse. Of the remaining 12 patients who were observed after dissection only 1 (8 per cent) had relapse. In group II 19 of 31 patients were treated with initial chemotherapy: 13 (68 per cent) achieved a complete response, while 6 required retroperitoneal lymph node dissection after chemotherapy. Of 31 patients 12 were treated with initial retroperitoneal lymph node dissection and 9 (75 per cent) received post-dissection chemotherapy. In group III 5 of 7 patients were treated with initial retroperitoneal lymph node dissection and 3 of the 5 subsequently required chemotherapy. Of the 7 patients 2 received initial chemotherapy and achieved a complete response. All 56 patients are without disease at 4+ to 106+ months (median 28 months). We conclude that patients with the characteristics of groups II and III should be managed initially with chemotherapy, with retroperitoneal lymph node dissection reserved for patients who fail to achieve a complete response. In group I retroperitoneal lymph node dissection is sufficient initial treatment if pathological evaluation of the retroperitoneal lymph nodes does not meet our criteria for post-dissection adjuvant chemotherapy.
Antineoplastic Combined Chemotherapy Protocols↗
Phase I/II study of recombinant interferon gamma in advanced renal cell carcinoma.
A phase I and II evaluation of 42 patients with advanced renal cell carcinoma treated with recombinant interferon gamma was done. Patients were treated with either a daily 2-hour infusion or 24-hour infusion for 7 days every 3 weeks for at least 2 cycles. Patients who demonstrated stable disease or improvement on therapy then were continued on a maintenance program of 5 days of recombinant interferon gamma administered every 3 to 4 weeks. The initial starting dose was 10 mcg. per m.2 per day with escalations to 30, 100, 300, 1,000 and 3,000 mcg. per m.2. Dose-limiting toxicity occurred at 1,000 to 3,000 mcg. per m.2, and included leukopenia, chills, fevers, rigors and hepatotoxicity as manifested by elevation in the transaminase and bilirubin levels. Tumor responses were seen initially at the 300 mcg. per m.2 dose level. Over-all, of 41 patients evaluable for therapeutic effectiveness 1 demonstrated a complete response 6 months in duration and 3 demonstrated partial responses 2, 9 and 13 months in duration. However, 6 patients demonstrated organ site responsiveness, including resolution of pulmonary lesions (2 complete and 1 partial responses), lymphadenopathy (1 complete and 1 partial responses), a pleural-based lesion in 1 patient with a partial response and complete resolution of hepatic metastases in 1 patient. We conclude that recombinant interferon gamma at a dose of 1,000 to 3,000 mcg. per m.2 for 7 days and repeated every 2 to 3 weeks had demonstrable anticancer activity in patients with metastatic renal carcinoma.
Adult↗
Silicone lymphadenopathy in a long distance runner: complication of a silastic prosthesis.
A 33-year-old male runner, who had undergone a Swanson silastic prosthetic implant for degenerative joint disease of the first metatarsal head and proximal phalanx of the right great toe, presented with unilateral inguinal lymphadenopathy. Biopsy revealed confluent, non-caseating granulomas containing silastic material. Silicone lymphadenopathy is unusual and most frequently presents as axillary adenopathy in patients with rheumatoid arthritis as a sequelae of prosthetic surgery. This case is clinically distinctive for its site of presentation in a healthy athlete and is histologically remarkable for the marked granulomatous response to the silastic elastomers.
Adult↗
Gonadotropin-releasing hormone analogs and prostatic cancer.
Analogs of GnRH constitute a new category of drugs available for the treatment of advanced prostatic cancer. The efficacy and safety of GnRH analogs in the treatment of this disease is now well established. These compounds represent an important alternative therapy for advanced prostatic cancer patients who do not wish to undergo orchiectomy or for whom DES is not tolerable because of the risk of cardiovascular complications. The advent of the monthly depot form of these drugs will make treatment more convenient and less invasive and will enhance patient compliance.
Androgen Antagonists↗
Failure patterns of nonseminomatous testicular germ cell tumors: radiographic analysis of 51 cases.
A retrospective analysis was performed of 51 consecutive cases of treatment failure (tumor recurrence) of nonseminomatous germ cell tumors. Twelve patients with clinical stage I disease relapsed after lymph node dissection; 39 with stage II or III disease relapsed after chemotherapy. Routine follow-up consisted of monthly chest radiography and determination of serum tumor marker levels (alpha-fetoprotein and human chorionic gonadotropin), as well as abdominal computed tomography every 6 months. The median recurrence interval was 3 months; 96% of the relapses occurred within 2 years. In 61% of patients, recurrence was in the initial disease site only, in 26% it was in both new and initial sites, and in 13% it was in new sites only. At the time of treatment failure, 47 (92%) of the patients had positive radiologic studies and 44 (86%) had positive serum marker levels. Nine (18%) had positive radiologic studies only, and four (8%) had positive serum marker levels only. The analysis demonstrated the complementary role of radiologic studies and serum tumor-marker assays in detecting treatment failure.
Adolescent↗
Clinical stage I carcinoma of the testis: a review.
Significant advances in the management of disseminated carcinoma of the testis have had a tremendous influence on the management of all stages of disease, including both stage I and stage II. Because the disease is so uniformly curable in advanced forms, strategies have evolved for lower stages of disease to maximize curative potential with minimization of therapeutic intervention and potential long-term side effects. This review addresses issues of diagnosis and initial clinical staging of patients with stage I carcinoma of the testis. The usefulness of biological tumor markers and the accuracy, sensitivity, and specificity of radiographic imaging modalities are emphasized. The traditional treatment of stage I seminomas and nonseminomas includes the role of both radiation therapy and retroperitoneal lymph node dissection (RPLND). Treatment results and complications of each modality are also reviewed. The importance of orchiectomy followed by meticulous surveillance, as well as a critical analysis of prognostic features of subsequent locoregional or systemic relapse in patients with stage I testis cancer, focuses attention on changing concepts of this disease. The rationale underlying improved ability to stage patients meticulously and offer therapeutic intervention when necessary following orchiectomy, constitutes the focus of present and future clinical research. Such strategies are discussed in detail.
Biomarkers, Tumor↗
Late toxicities, long-term follow-up, less intensive treatment: leading issues in the therapy of testis cancer.
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Antineoplastic Combined Chemotherapy Protocols↗
Stage I nonseminomatous germ cell testicular tumor: prediction of metastatic potential by primary histopathology.
A study of 60 patients with clinical stage I nonseminomatous germ cell testicular tumor (NSGCT) was conducted to identify prognostic factors that may predict the likelihood of metastasis. Clinical features and histopathologic features of the primary testicular tumor were examined and analyzed for correlations with the presence of retroperitoneal nodal metastasis documented by surgery (N+) and with development of relapse (R+). Pathologic tumor stage greater than or equal to 2, with tumor extension into the tunica albuginea, rete testis, epididymis, or spermatic cord, was correlated with an increased rate of N+ compared with pathologic tumor stage I (P = .001). Vascular invasion was correlated with a higher rate of N+ (P = .05) and had a similar association with R+ (P = .08). Tumors containing less than 50% teratoma were found to have a higher rate of N+ than tumors with greater than or equal to 50% teratoma (P = .02). Based on the identified prognostic factors, a model for predicting the probability of retroperitoneal nodal metastasis in clinical stage I patients is proposed. The risk factors for nodal metastasis are: pathologic tumor stage greater than or equal to 2, vascular invasion, and less than 50% teratoma. Patients with none of the risk factors are considered at low risk and may be offered orchiectomy alone with surveillance for initial treatment. Patients with all three risk factors are at high risk and should be treated with a retroperitoneal lymph node dissection (RPLND) or possibly chemotherapy. Patients with one or two risk factors are at intermediate risk; it is recommended that they undergo RPLND. This risk model facilitates a rational approach to the management of clinical stage I NSGCT.
Adult↗
Acute pancreatitis associated with chemotherapy for germ cell tumors in two patients.
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Acute Disease↗
Management of patients with clinical stage I or II nonseminomatous germ cell tumors of the testis. Evolving therapeutic options.
Eighty patients with clinical stage I or II nonseminomatous germ cell tumors of the testis were managed with modified protocols, including modified nerve-sparing retroperitoneal lymph node dissection for patients with stage I cancer, retroperitoneal lymph node dissection for patients with low-volume stage II cancer, and initial chemotherapy with or without subsequent retroperitoneal lymphadenectomy for patients with high-volume stage II cancer. Patients with low-stage disease (clinical stage I) were treated successfully with modified retroperitoneal lymph node dissection (relapse rate, three of 40 patients). Clinical understaging was evidenced in 14 of 48 patients with clinical stage I disease who were found to have pathologic involvement of the retroperitoneal lymph nodes, including six patients with extensive retroperitoneal nodal involvement (pathologic stage B2). Of nine patients with retroperitoneal tumors less than 3 cm in diameter, four patients were satisfactorily treated with retroperitoneal lymph node dissection alone while five patients required chemotherapy after retroperitoneal lymph node dissection. Of 26 patients with retroperitoneal tumors 3 to 5 cm in diameter, 17 patients were treated with chemotherapy alone. All patients remain free of disease after the completion of definitive therapy. We conclude that therapeutic options should be modified based on histologic factors in the primary tumor, extent of retroperitoneal disease as indicated on a computed tomographic scan, and presence or absence of elevated tumor markers. By consideration these factors, optimum therapy can be selected to achieve the highest long-term survival rate with the least morbidity.
Antineoplastic Combined Chemotherapy Protocols↗
Cavitary lung nodules associated with combination chemotherapy containing bleomycin.
We describe a patient in whom multiple cavitary lung nodules developed without infectious symptoms after treatment with bleomycin, cisplatin and vinblastine combination chemotherapy for metastatic testis cancer. Open lung biopsy demonstrated extensive granuloma formation without evidence of malignancy or infection. This report extends the spectrum of bleomycin pulmonary toxicity to include cavitary pulmonary nodules associated with granuloma formation.
Antineoplastic Combined Chemotherapy Protocols↗
Pulmonary emboli as a complication of germ cell cancer treatment.
A total of 3 patients with germ cell cancer had pulmonary emboli while receiving cisplatin-containing chemotherapy. In addition to cisplatin, 1 patient was receiving etoposide plus doxorubicin, 1 vinblastine plus bleomycin and 1 etoposide plus bleomycin at the time of the vascular event. One patient died of cardiovascular collapse, while the other 2 presented with severe shortness of breath, hemoptysis and pleuritic chest pain. A review of vascular complications of cisplatin-containing chemotherapy is presented. Awareness and early recognition of pulmonary emboli in patients receiving these chemotherapeutic agents may minimize treatment-related morbidity and mortality.
Adult↗
Appropriate endpoints for superficial bladder cancer clinical trials.
Many protocols for treatment of superficial bladder cancer include periodic cystoscopic examinations with resection of visible lesions. This allows pathological restaging of the disease at each examination. For example, this type of follow-up is common in clinical trials evaluating intravesical therapies. In such trials, clinical outcome is typically summarized using end-points that measure failure to control superficial disease. Alternative endpoints measuring failure to prevent progression to invasive disease are often ignored. In this report, the rationale for ignoring the invasive disease endpoints is given and flaws in the rationale are described. Evidence from actual data sets support the view that superficial disease endpoints may not be appropriate surrogates for invasive disease endpoints. It is recommended that time to invasive disease should be considered a major endpoint when designing and analyzing trials in superficial bladder cancer.
Clinical Trials as Topic↗
Detection of retroperitoneal metastases in early-stage nonseminomatous testicular cancer: analysis of different CT criteria.
To determine the predictive values of using different sizes on CT as criteria for the detection of retroperitoneal lymph-node metastases in patients with early-stage (nodes 5 cm or less in diameter) primary nonseminomatous testicular cancer, we performed a retrospective analysis of 51 patients. Measurements of lymph-node transaxial diameters on CT were correlated with histologic findings at lymph-node dissection or with response to initial chemotherapy. All patients had normal serum markers (alpha-fetoprotein, human chorionic gonadotropin) after orchiectomy. The frequency of lymph-node metastases in this population was 51%. When a CT criterion of 5 mm was used, the negative predictive value was 79%; the positive predictive value, 62%; the specificity, 44%; and the sensitivity, 88%. With a criterion of 15 mm, the negative predictive value was 63%; the positive predictive value, 71%; the specificity, 76%; and the sensitivity, 58%. Metastases in retroperitoneal lymph nodes that appeared within normal limits (i.e., had normal transaxial diameters) on CT were the limiting factor in the ability of CT to exclude the presence of metastases. We conclude that using smaller sizes on CT scans as the criteria for detection of lymph-node metastases cannot replace dissection of nodes in patients who have normal-sized nodes but may be helpful in identifying a subgroup of patients who are at lower risk of harboring metastases when treatment by orchiectomy alone is considered.
Humans↗