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Biomedical subjects

S D Williams

Publications and source records attributed to S D Williams.

At least 109 records · Page 6Linked to original sources
PubMed1986

VP-16 plus ifosfamide plus cisplatin as salvage therapy in refractory germ cell cancer.

Forty-eight evaluable male patients with germ cell tumors (GCT) failing to be cured with first-line therapy were treated with VP-16 (75 mg/m2), ifosfamide (1.2 g/m2), and cisplatin (20 mg/m2) (VIP), all given daily for 5 consecutive days every 3 weeks. All patients either achieved an unresectable partial remission as their best response to induction chemotherapy (Group A), relapsed from complete remission (CR) less than or equal to 2 months after induction therapy (Group B), or had received cisplatin plus VP-16 as previous salvage therapy (Group C). Nine (19%) had extragonadal GCT, and 37 (77%) had advanced disease. Twenty-three (48%) of the patients had greater than or equal 2 prior treatment regimens. Sixteen of 48 (33%) achieved CR with VIP treatment alone or following surgical excision of residual disease. Six of 22 (27%), three of seven (43%), and seven of 19 (37%) patients from groups A, B, and C, respectively, attained a CR. The median survival time of all patients was 7 months (range 0 to 28+) with seven patients remaining continuously free of disease (four patients greater than 1 year). Myelosuppression was significant with a median WBC nadir of 900/mm2 and platelet nadir of 24,000/mm2. Fourteen (26%) had granulocytopenic fever, and renal insufficiency developed in 15%. VIP combination chemotherapy demonstrates activity in this highly unfavorable population of patients with germ cell tumors. The actual contribution of ifosfamide in this regimen is unclear, but these results compare favorably to our experience with similar patients treated with cisplatin plus VP-16 alone. Further studies with VIP as initial salvage therapy for patients with GCT are planned.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Random prospective study of vindesine versus vindesine plus high-dose cisplatin versus vindesine plus cisplatin plus mitomycin C in advanced non-small-cell lung cancer.

In this phase III randomized study, 124 evaluable patients with unresectable non-small-cell lung cancer (NSCLC) were randomized to vindesine v cisplatin (120 mg/m2) plus vindesine v cisplatin (60 mg/m2) plus vindesine plus mitomycin C. The objective response rate for cisplatin and vindesine was 27% v 20% for cisplatin, vindesine, and mitomycin C, and 14% for vindesine alone (P = .25 for cisplatin and vindesine v vindesine). The percentage of patients having stable disease (no progression for a minimum of 3 months) was 20% (cisplatin and vindesine), 27% (cisplatin, vindesine, and mitomycin C), and 26% (vindesine alone), respectively. The median survival time for vindesine was 18 weeks, compared with 26 weeks for cisplatin and vindesine and 17 weeks for cisplatin, vindesine, and mitomycin C. Overall survival was not statistically different for cisplatin plus vindesine v vindesine (P = .65). There was no evidence for improved duration of remission or survival of responders with the cisplatin (120 mg/m2) and vindesine arm. This study failed to demonstrate sufficient therapeutic benefit for cisplatin and vindesine (+/- mitomycin C) compared with single-agent vindesine to justify the increased cost and toxicity of these combination regimens.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Resection of thoracic and abdominal teratoma in patients after cisplatin-based chemotherapy for germ cell tumor. Late results.

Fifty-one patients with primary testicular (N = 46) or mediastinal germ cell cancer (N = 5) were treated from April, 1975, through May, 1981, and had teratoma resected from residual disease after cisplatin-based combination chemotherapy. All patients had normal serum markers before resection of pulmonary (N = 12), mediastinal (N = 5), thoracoabdominal (N = 8), supraclavicular (N = 1) or abdominal disease (N = 25). Teratoma was classified as mature teratoma (N = 29), immature teratoma (N = 15), or immature teratoma with non-germ cell elements (N = 7). Thirty of 51 (60%) patients remain free of recurrent disease, whereas 20 patients have either recurrent carcinoma (N = 10) or teratoma (N = 10). One patient has a presumed second malignancy. After additional chemotherapy, four patients with recurrent carcinoma are alive and disease free and six have died. After an additional operation, eight of 10 patients with recurrent teratoma are long-term survivors. In four patients the initial relapse of carcinoma developed more than 2 years after therapy; in an additional patient carcinoma recurred after a 32 month disease-free survival period. Univariate factors predicting for relapse include tumor burden, immature teratoma with non-germ cell elements, and site (mediastinum), whereas only immature teratoma with non-germ cell elements and site predicted for survival. Immature teratoma and mature teratoma had similar relapse-free intervals and overall survival intervals. According to a multivariate analysis, primary tumor site at the mediastinum is the most significant adverse factor predictive for both relapse and survival (two of five patients survived). This study appears to support the various preclinical models that demonstrate multipotential capabilities of teratoma. Complete surgical excision of teratoma remains the most effective treatment with continued close follow-up recommended for high-risk patients (immature teratoma with non-germ cell elements, large tumor burden, or primary mediastinal tumors.

Abdominal Neoplasms↗
PubMed1986

Phase II study of etoposide for carcinoma of the prostate.

The treatment of prostate carcinoma with the epipodophyllotoxin derivative etoposide was studied in a multi-institutional phase II trial. An iv dose schedule of 130 mg/m2 daily for 3 days every 3 weeks was utilized. A total of 36 patients were evaluable; the observed total response was 3%. Moderate toxicity (predominantly myelosuppression) was seen utilizing this treatment schedule. It is concluded that etoposide possesses little single-agent therapeutic activity for prostate carcinoma.

Blood Cell Count↗
PubMed1986

Phase II evaluation of doxorubicin plus cisplatin in advanced thyroid cancer: a Southeastern Cancer Study Group Trial.

Twenty-two evaluable patients with all cell types of advanced thyroid cancer were treated with the combination of doxorubicin (60 mg/m2) plus cisplatin (60 mg/m2). There were two brief partial remissions (9.1%). There was considerable toxicity, with one drug-related death. Combination chemotherapy as given in this study was not effective for this patient population.

Adult↗
PubMed1985

Modified neck dissection for metastatic testicular carcinoma.

Carcinoma of the testicle is a unique clinicopathologic entity in that an optimistic attitude toward cure can be entertained even in the presence of distant metastasis. Chemotherapy, followed by an aggressive surgical resection of residual disease, can result in eradication of this neoplasm. This tumor is capable of being monitored by the use of serum markers, namely, human chorionic gonadotropin and alpha-fetoprotein. After induction chemotherapy, the transition of elevated serum tumor markers to normal levels suggests that malignant disease has been eliminated or converted to teratoma. Elevated markers indicate persistent or recurrent carcinoma and mandate further chemotherapy. If normalization of tumor markers occurs, any residual mass in the abdomen, chest, or neck should be surgically resected. The otolaryngologist plays a role in the diagnosis and the resection of residual neck disease. Metastatic testicular carcinoma can present as a supraclavicular neck mass and must be considered in the differential diagnosis of a mass in this area. Large residual neck lesions are best removed through the exposure afforded by modified neck dissection.

Adolescent↗
PubMed1985

Phase II study of mitoxantrone in advanced squamous cell carcinoma of the head and neck. A Southeastern Cancer Study Group trial.

A phase II study of mitoxantrone in squamous cell carcinoma of head and neck origin was conducted. Fifty-three evaluable patients were treated with this agent at a dosage of 5 mg/M2/week. The majority of patients were of high performance status. Twenty-seven patients had received previous chemotherapy plus surgery and/or radiotherapy. Twenty-six had not been treated with chemotherapy previously although thirteen of these patients had prior radiotherapy and surgery, eight radiotherapy only, one surgery only, and four no previous treatment. There was only one objective response. Toxicity was relatively mild, although 45% of the patients at some time experienced at least moderate leukopenia. Further studies of this agent in this disease are not warranted.

Anthraquinones↗
PubMed1985

Cisplatin, vinblastine, and bleomycin as second-trial therapy in ovarian carcinoma. A pilot study of the Gynecologic Oncology Group.

Ten patients with ovarian carcinoma whose tumors had progressed on first-trial chemotherapy were treated with cisplatin, vinblastine, and bleomycin (PVB) to determine the efficacy, dose range, and toxicity of this combination. Two dose levels of vinblastine were used. Objective responses occurred in 5/10 patients (3 CR, 2 PR), with a median response duration of 17.0 weeks. Toxicity was appreciable. One patient expired of bleomycin-induced pulmonary fibrosis. With the higher dose of vinblastine, four patients had grade III and three patients had grade IV hematologic toxicity. At the lower dose, two patients had grade II and one patient had grade III hematologic toxicity. PVB has activity in second-trial therapy of ovarian carcinoma at the dose and schedule tested, but the role of this regimen in the future treatment of this disease remains to be determined.

Adenocarcinoma↗
PubMed1985

Dental caries and dental treatment in the primary dentition in an industrialized South African community.

This paper reports an examination of dental caries in the primary dentition of 2-5-yr-old white children in an industrialized South African city, in 1981 and 1983. There was a decrease in dental caries prevalence over the 2-yr period accompanied by an increase in dental treatment in 3-5-yr-olds. Treatment, however, remains low. Socioeconomic status had a varying effect on the trends, but in general there was a greater reduction in dental caries in the lower socioeconomic areas.

Child, Preschool↗
PubMed1985

Ifosfamide: an active drug in the treatment of adenocarcinoma of the pancreas.

From April 1982, until February 1984, 29 patients with biopsy-proven and measurable adenocarcinoma of the pancreas were treated with ifosfamide. Ifosfamide was administered at a dose of 1.25 to 1.5 g/m2 daily for five consecutive days with courses repeated every three weeks. If no serious toxicity was noted, subsequent dosages were escalated to a maximum of 2.0 g/m2/d. In addition, N-acetylcysteine (NAC) (8 to 12 g/d) was administered (in divided daily doses days 1 through 7) as a urothelial protective agent. Nausea and vomiting occurred in the majority of the treated patients. Other toxicities noted were mild myelo-suppression, CNS toxicity, and one case of acute renal failure. One complete response (CR) and five partial responses (PR) were observed in 27 evaluable patients (CRs and PRs = 22%). Ifosfamide has definite activity against pancreatic adenocarcinoma. Doses greater than 1.2 g/m2 for days 1 through 5 can be administered without significant toxicity in the majority of patients. Further trials with ifosfamide alone and/or with other agents are warranted.

Acetylcysteine↗
PubMed1985

Successful treatment of resistant germinal neoplasms with VP-16 and cisplatin: results of a Southeastern Cancer Study Group trial.

Between July 1979 and May 1982, we treated 45 male patients with refractory germinal neoplasms. All patients had previously received intensive cisplatin-containing combination chemotherapy regimens. Patients received salvage chemotherapy with VP-16 and cisplatin +/- bleomycin +/- doxorubicin. Of 44 evaluable patients, 19 (43%) achieved complete remissions with salvage chemotherapy, 12 (27%) had partial remissions, and nine (21%) had no response. Four patients (9%) were not evaluable for response due to early death or noncompliance but are considered treatment failures. Ten patients (23%) remain alive and continuously disease free 20 to 39 months (median, 29 months) after completion of therapy. Hematologic toxicity was severe, with one death related to sepsis. Bleomycin-induced pulmonary fibrosis occurred in 17 patients with two fatalities. The addition of bleomycin and/or doxorubicin to this regimen increases toxicity and probably does not improve treatment results. Salvage chemotherapy with VP-16 and cisplatin offers potentially curative therapy to men with resistant germinal tumors.

Actuarial Analysis↗
PubMed1985

Hematologic malignancies associated with primary mediastinal germ-cell tumors.

Three men with primary mediastinal germ-cell tumors subsequently developed a malignant hematologic disorder characterized by pancytopenia and marrow infiltration with hematopoietic blast cells. Two of these patients were classified as having acute megakaryocytic leukemia and the third was believed to have a myelodysplastic syndrome with a prominent megakaryocytic component. Analysis of clinical characteristics of these patients and review of the literature suggest that the proximate association of mediastinal germ-cell tumors with malignant hematologic disorders is neither a coincidence nor a consequence of chemotherapy given for the germ-cell tumor. We believe this association represents the evolution of a neoplastic disorder that initially involves a totipotent germ cell. These germ cells, when located in the mediastinum, apparently acquire hematologic phenotypes and are manifested clinically as a hematologic malignancy.

Acute Disease↗
PubMed1985

Cisplatin plus 5-FU for the treatment of adenocarcinoma of the colon.

Cisplatin plus 5-FU appears to have significant additive activity in various tumors, such as head and neck carcinoma and esophageal cancer. A partial explanation for this may be drug synergism, which has been noted in the L1210 leukemia model. Based on these data, a prospective trial of weekly bolus 5-FU (15 mg/kg) and cisplatin (60 mg/m2) given every 3 weeks was initiated at Indiana University. Forty-one patients, of whom 38 are fully evaluable for response, were treated with these two drugs. Ten partial and one complete response (complete + partial response rate = 29%) were observed in the 38 evaluable patients. Thirteen additional patients had stable disease for greater than or equal to 3 months. The median durations of remission and survival time were 6 and 10.3 months, respectively. Myelosuppression was unusually severe, with granulocyte counts less than 1000/mm3 in 65% of patients, including four patients with granulocyte count nadirs less than 100/mm3. Three patients developed granulocytopenic fever, with two drug-related deaths (sepsis, hyperosmolar coma). Nearly all patients had nausea and vomiting, but this was not a treatment-limiting toxic effect in any patient. Although this combination suggests a higher response rate than usually seen with bolus iv 5-FU in colon cancer, a trial comparing 5-FU alone or with cisplatin to determine whether true synergy exists is currently underway.

Adenocarcinoma↗
PubMed1984

The development of non-germ cell malignancies within germ cell tumors. A clinicopathologic study of 11 cases.

Eleven male patients had germ cell tumors of the testis (7), mediastinum (3), or retroperitoneum (1) in which non-germ cell malignancies developed. Such malignant non-germ cell elements were present in the primary excisions of five patients and were subsequently found in additional resected tissue in 10 of 11 patients. In the patients who had multiple pathology specimens examined, a progression from atypia to predominant non-germ cell malignancy was often found. The authors believe these malignant elements arose within teratomatous foci, since eight of nine cases had teratoma in the primary tumor, and teratoma was found in subsequently resected tissue in one additional case. Cisplatin therapy frequently "unmasked" the non-germ cell malignant elements by destroying the more chemosensitive germ cell cancers. The prognosis was worst for five patients who developed progressive embryonal rhabdomyosarcoma: two of these patients died of local spread of tumor, whereas a third died of metastatic sarcoma. Only one patient, who had total surgical excision of rhabdomyosarcoma, survived. Other forms of sarcoma that developed within germ cell tumors did not appear to adversely affect the prognosis beyond that of teratoma. It is currently recommended, when feasible, that patients with teratoma and sarcoma undergo total surgical excision. Further treatment with cisplatin regimens, after eradication of the germ cell component, has not been helpful. The role of other forms of chemotherapy remains speculative.

Adolescent↗