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Biomedical subjects

S D Williams

Publications and source records attributed to S D Williams.

At least 91 records · Page 5Linked to original sources
PubMed1989

Use of carboplatin in the treatment of testicular cancer.

Recent evidence indicates that carboplatin may be useful in the treatment of various forms of testicular cancer. The results of one study showed that carboplatin was highly effective and well tolerated in patients with previously untreated disseminated seminoma. However, conventional doses of carboplatin appear to be inactive in patients with refractory nonseminoma. Of particular interest are recent results showing that an intensive regimen of carboplatin in combination with etoposide with autologous bone marrow rescue will induce a few complete remissions in heavily pretreated germ cell tumor patients.

Antineoplastic Agents↗
PubMed1988

Testicular cancer: the quest continues.

Treatment for testicular cancer has dramatically improved during the last 15 years. Much of this success has come about because of improved staging and operative techniques but, most importantly, through the introduction of successful systemic chemotherapy. Nonetheless, relevant issues still remain to be addressed in regard to the optimal therapy for patients with germ cell neoplasms. Included in these issues is delineating the most effective but minimally morbid treatment for patients with early-stage and low-volume metastatic disease while continuing to create innovative treatment approaches for poor-risk patients with metastatic disease. The unique association of primary mediastinal germ cell neoplasms with the development of non-germ cell cancers and Klinefelter's syndrome may provide some early clues for the determination of factors controlling differentiation. These observations issue a challenge to both clinical and preclinical researchers involved in the study of this neoplasm.

Combined Modality Therapy↗
PubMed1988

Salvage therapy in recurrent germ cell cancer: ifosfamide and cisplatin plus either vinblastine or etoposide.

STUDY OBJECTIVE: To determine the efficacy of the addition of ifosfamide to cisplatin plus etoposide (VIP), or vinblastine (VeIP), in patients with recurrent germ cell tumors. DESIGN: Nonrandomized, prospective phase II trial. SETTING: Tertiary referral university hospital. PATIENTS: Fifty-six of fifty-eight entered patients with measurable and progressive recurrent germ cell tumors of testicular (46 patients), ovarian (1 patient), and extragonadal (9 patients) origin were evaluable for response after not being cured with cisplatin, vinblastine, and etoposide regimens. INTERVENTIONS: Patients were administered cisplatin (20 mg/m2 body surface area daily for 5 days), ifosfamide (1.2 g daily for 5 days), plus either etoposide (75 mg daily for 5 days) or vinblastine (0.11 mg/kg body weight on days 1 and 2). In addition, vigorous intravenous hydration therapy with normal saline (100 to 125 mL/h) was administered during the treatment course. Uroepithelial protective agents, N-acetylcysteine (orally) or mesna (intravenously), were administered. Four courses were administered to responding patients every 3 weeks. When complete excision was feasible, surgical resection of residual tumor was done approximately 6 to 8 weeks after chemotherapy. MEASUREMENTS AND MAIN RESULTS: Twelve of fifty-six evaluable patients had a complete remission with chemotherapy alone, whereas 8 additional patients were free of disease after resection of teratoma (3 patients) or carcinoma (5 patients) for a total disease-free rate of 36% (95% CI, 23.4 to 49.6). The 95% CI median duration of remission for these patients is 34 months (range, 3 to more than 42; 95% CI, 9 months to infinity), and the median survival for all eligible patients is 12.7 months (95% CI, 10 months to 26 months), with 15 of the 20 patients who achieved disease-free status alive 18 to 53 months or more. Nine of fifty-eight patients remain free of disease, including 7 patients for 2 years or longer. Hematologic and nephrotoxicity were the predominant drug-related toxicities, with one drug-related death secondary to pneumonia. CONCLUSIONS: Ifosfamide combination chemotherapy as third-line or greater therapy can produce durable complete remissions in heavily pretreated patients with recurrent germ cell tumors.

Adolescent↗
PubMed1988

Cisplatin-based combination chemotherapy for disseminated germ cell tumors: long-term follow-up.

A retrospective analysis of the initial 229 cases of disseminated germ cell tumors treated at Indiana University with cisplatin, vinblastine, and bleomycin (PVB), with or without doxorubicin revealed 146 patients who are alive and disease-free with a minimum follow-up of 6 years and a median follow-up of 8.5 years. At 12 years, the estimated probability of survival is 65.0%, and the estimated probability of relapse-free survival for complete responders is 83.5%. Long-term complications, such as clinically significant organ toxicity or therapy-related second malignancies, have not been observed. The functional status of survivors is maintained, with 95% returning to their pretherapy status, of which 88% are fully employed. Of patients receiving chemotherapy without abdominal surgery, 35% have fathered healthy children posttherapy. Achievement of complete remission (CR) in disseminated germ cell tumors with cisplatin-based combination chemotherapy translates to long-term disease-free survival and cure for the majority of patients, with preservation of functional status.

Adolescent↗
PubMed1987

Immediate adjuvant chemotherapy versus observation with treatment at relapse in pathological stage II testicular cancer.

Between 1979 and 1984, 195 evaluable patients were entered in an international multicenter study comparing two regimens for patients with completely resected pathological Stage II testicular cancer (that is, with positive retroperitoneal lymph nodes). All patients had undergone orchiectomy and dissection of the retroperitoneal lymph nodes. They were randomly assigned to be treated with two cycles of immediate adjuvant cisplatin-based chemotherapy or to be observed monthly with treatment at relapse. The median follow-up period was four years. Of the 97 patients assigned to adjuvant chemotherapy, 6 (6 percent) had a recurrence; however, only 1 had received adjuvant chemotherapy before the recurrence. Three died (one of testicular cancer), and 94 of the 97 survived. Of the 98 patients who were observed, 48 (49 percent) had a relapse. However, almost all patients with relapses were effectively treated, and 93 of the 98 are alive and disease-free; 3 have died of testicular cancer. No identifiable factors were strongly associated with the risk of relapse. We conclude that two courses of cisplatin-based adjuvant chemotherapy will almost always prevent relapse in pathological Stage II testicular cancer treated with orchiectomy and retroperitoneal-lymph-node dissection. However, when surgery, follow-up, and chemotherapy are optimal, observation with chemotherapy only for relapse will lead to equivalent cure rates.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Treatment of disseminated germ-cell tumors with cisplatin, bleomycin, and either vinblastine or etoposide.

Standard chemotherapy for disseminated germ-cell tumors includes a combination of cisplatin, vinblastine, and bleomycin, but this regimen produces substantial neuromuscular toxicity. In a randomized clinical trial in 261 men with disseminated germ-cell tumors, we substituted etoposide for the vinblastine in this regimen in half the patients to compare the efficacy and toxicity of the two treatments. Among 244 patients who could be evaluated for a response, 74 percent of those receiving the regimen including vinblastine and 83 percent of those receiving the regimen including etoposide became disease-free with or without subsequent surgery (P not significant). Among the 157 patients with high tumor volume, 61 percent became disease-free on the regimen that included vinblastine, as compared with 77 percent on the regimen that included etoposide (P less than 0.05). Survival among the patients who received etoposide was higher (P = 0.048). The regimens were similar in terms of myelosuppressive effects and pulmonary toxicity. However, the etoposide regimen caused substantially fewer paresthesias (P = 0.02), abdominal cramps (P = 0.0008), and myalgias (P = 0.00002). We conclude that etoposide with cisplatin and bleomycin is superior to vinblastine with cisplatin and bleomycin in the treatment of disseminated germ-cell tumors because of diminished neuromuscular toxicity and, among patients with advanced disease, better efficacy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

The significance of atypia within teratomatous metastases after chemotherapy for malignant germ cell tumors.

The completely resected teratomatous metastases of 55 patients who had been treated with cisplatin-based combination chemotherapy for non-seminomatous germ cell tumors were reviewed to see if cellular atypia had an effect with respect to recurrent disease. The degree of atypia of the epithelial and mesenchymal elements was assessed on the basis of the cytologic features and mitotic activity. Twenty-three percent of the cases contained high-grade epithelial elements, whereas high-grade mesenchymal elements occurred in 18% of the cases; in addition there were nine cases classified as showing frankly malignant teratomatous elements. The presence of cytologically disturbing epithelial and mesenchymal elements (which, however, lacked an invasive malignant pattern) correlated with an increased incidence of recurrent teratoma compared to less atypical teratomatous elements (23% vs. 6% for epithelial elements, and 18% vs. 9% for mesenchymal elements, respectively). This difference, however, was not statistically significant (P greater than 0.05). There was no correlation between teratomatous atypia and recurrent, non-teratomatous germ cell tumor. The presence of an invasive malignant pattern did identify patients at significantly increased risk for recurrent teratoma-derived tumor. The authors conclude that cytologic atypia in the absence of invasion is not sufficient justification for altering the usual therapeutic strategies for patients with teratomatous metastases.

Adolescent↗
PubMed1987

Chemotherapy of metastatic seminoma: the Southeastern Cancer Study Group experience.

From 1978 to 1984, 62 patients with advanced seminoma of testicular or extragonadal origin were entered on two consecutive Southeastern Cancer Study Group (SECSG) protocols. All patients had progressive disease and were stratified according to tumor burden. Randomization on SEG 78-GU240 was cisplatin, vinblastine, and bleomycin (PVB), with or without doxorubicin; on SEG 81-GU332, randomization was to PVB or cisplatin, etoposide (VP-16), and bleomycin (PVP16B). Dosages of etoposide, vinblastine, and doxorubicin were decreased by 25% in patients who had received prior radiotherapy. Thirty patients (55%) had received prior chest and/or abdominal radiotherapy. Overall, 41 of 60 evaluable patients (68%) achieved a complete remission (CR) and 37 patients are alive and free of disease. CR was obtained in 13 of 15 patients (87%) with minimal disease, 13 of 16 (81%) with moderate disease, and 15 of 29 (52%) with advanced disease. Patients with no prior radiotherapy or limited-field (chest or abdomen) radiotherapy were more likely to achieve CR than those with prior chest and abdominal radiotherapy (75% v. 42%). Using univariate analysis, the extent of disease is the only significant prognostic factor, whereas both extent of disease and extent of prior radiotherapy are significant in a multivariate analysis. This study confirms the chemosensitivity of metastatic seminoma in a cooperative group setting and defines prognostic factors useful for comparison of other chemotherapeutic trials in seminoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Klinefelter's syndrome associated with mediastinal germ cell neoplasms.

Several case reports have suggested an association of primary mediastinal germ cell tumor (PMGCT) and Klinefelter's syndrome (KS). In an effort to confirm this association, 22 patients with mediastinal germ cell tumors had chromosome studies performed in a prospective fashion. Five patients (22%) had karyotypic or pathologic evidence of KS. All of the patients with KS had germ cell tumors of the nonseminomatous subtype and were relatively young (median age, 15 years). The literature confirms the findings of a young median age (18 years), nonseminomatous subtype, and mediastinal location of the germ cell neoplasm. We conclude that patients with KS are predisposed to the development of mediastinal nonseminomatous germ cell cancers.

Adolescent↗
PubMed1987

Postchemotherapy resection of residual tumor in limited stage small cell lung cancer.

To determine the feasibility of post-chemotherapy resection of residual tumor in small cell lung cancer, 24 selected patients with limited-stage disease were evaluated for exploratory thoracotomy. All 24 patients achieved partial or complete clinical response to chemotherapy and were considered adequate medical candidates for surgical resection. Fifteen patients underwent a lobectomy or pneumonectomy, 13 of whom had residual tumor in the resected specimen. Of the nine remaining patients, seven had no tumor found on biopsy at thoracotomy and two had unresectable mediastinal node involvement. No chemotherapy was administered postoperatively in any patient until disease progression or relapse was documented. Median survival for the entire group was 19 months and did not differ according to the surgical procedure performed. Nineteen patients had relapse. Patients undergoing biopsy only recurred locally in six of seven cases a median of five months post-thoracotomy (range one to six months). Two "biopsy only" patients were tumor free at 34+ and 56+ months. Local recurrence was observed in six of 12 resected patients, while six patients experienced only extrathoracic metastases. Median time to recurrence for resected patients was also five months. Four resected patients experienced late recurrence 16 to 36 months postoperatively and were alive with tumor at 29+ to 42+ months. Two resected patients were tumor-free at 13+ and 37+ months. Post-chemotherapy surgical resection was feasible in limited-stage patients and improved local control of disease.

Antineoplastic Agents↗
PubMed1987

Status of chemotherapy for testis cancer.

Significant advances have been made in the treatment of advanced testicular cancer. These advances have been centered on better staging techniques with procedures such as computed tomography as well as the development of reliable serum markers. Based on these techniques, patients can be directed toward primary surgical therapy or systemic therapy. Cisplatin combination chemotherapy can be expected to cure approximately 80 per cent of all patients with advanced disease. Currently, cisplatin plus etoposide plus bleomycin is the standard treatment for patients with advanced disease. Newer trials are currently addressing the role of more aggressive therapy in patients with a poor prognosis while parallel trials examine the possibility of minimizing toxicity for those patients with good-risk disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Chemotherapy for head and neck cancer. Comparison of cisplatin + vinblastine + bleomycin versus methotrexate.

One hundred ninety-one patients with recurrent or metastatic squamous cell carcinoma of head and neck origin were allocated at random to chemotherapy with conventional-dose weekly intravenous methotrexate or the combination of cisplatin, vinblastine, and bleomycin. Methotrexate induced responses in 16 of 98 patients (16%), whereas 22 of 92 (24%) responded to the combination regimen (P = not significant). Remission duration (20.2 weeks methotrexate; 15.1 weeks combination) was similar on both arms, as was survival (31.4 weeks methotrexate; 29.0 weeks combination). Therapy was relatively well-tolerated on both treatment arms, although methotrexate produced more mucositis and the combination more gastrointestinal and renal toxicity. Response to chemotherapy and disease confined to the locoregional area were associated with somewhat longer survival. Combination chemotherapy as given in this study did not improve any observed parameter, and the results of treatment were poor in both arms.

Adult↗
PubMed1986

Teratoma following cisplatin-based combination chemotherapy for nonseminomatous germ cell tumors: a clinicopathological correlation.

From April 1975 through May 1981, 51 patients had teratoma resected from residual disease following cisplatin-based combination chemotherapy. All patients had normal serum markers before resection of abdominal (25), lung (12), mediastinal (5), thoracoabdominal (8) or other (1) disease. Teratoma was classified as mature in 29 cases, immature in 15 or immature with nongerm cell elements in 7. Of the 51 patients 31 (61 per cent) remain free of recurrent disease, while 20 either had recurrent carcinoma (10) or teratoma (10) requiring further therapy. Nine patients died, including 1 in whom angiosarcoma developed, which was thought to be secondary to previous radiation therapy. In 4 patients the initial relapse of carcinoma developed beyond 2 years after resection. Univariate factors predicting for relapse include tumor burden, immature teratoma with nongerm cell elements and site (mediastinum), while only immature teratoma with nongerm cell elements and site predicted for survival. Patients with immature teratoma had a comparable relapse-free and over-all survival as those with mature teratoma. Using a multivariate analysis, primary tumor site at the mediastinum was the most significant adverse factor predictive for relapse and survival. This study appears to support the various pre-clinical models that demonstrate multipotential capabilities of teratoma. Complete surgical excision of teratoma remains the most effective treatment with continued close followup recommended for high risk patients (immature teratoma with nongerm cell elements, large tumor burden and primary mediastinal tumors) with resected teratoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Ifosfamide in refractory male germ cell tumors.

We conducted a phase II clinical trial using ifosfamide (IFX) as a single agent in cisplatin-refractory male germ cell tumor. Thirty patients with measurable disease were treated with IFX, 2 g/m2 intravenously (IV) for 5 consecutive days every 3 weeks. N-acetylcysteine, 2 g orally every 4 hours, was given as a uroprotective agent. All patients had previously been treated with cisplatin, vinblastine, and bleomycin, and all except two also had previously received etoposide. There were six partial responses (PR) and one complete response (CR) for an overall objective response rate of 23%. The median duration of response was 3.5 months (range, 2 to 5.5 months). The median survival time was 3.5 months (range, 2 to 14+ months). The toxicity of the regimen consisted of hematuria (65% of the patients), nausea and vomiting (43%), neutropenia (WBC less than 2,000; 52%), thrombocytopenia (platelet count less than 50,000; 20%), and nephrotoxicity (12%). Hematuria was dose related, occurring in 48% of courses using 2 g/m2/d v only 5% of courses at lower doses. Serious nephrotoxicity (creatinine level greater than 6.0 mg/mL) was observed in three patients with an elevated pretreatment serum creatinine level. In conclusion, IFX is an active agent in this heavily pretreated population with advanced refractory germ cell tumor.

Acetylcysteine↗