Biomedical subjects

D J Adelstein

Publications and source records attributed to D J Adelstein.

At least 55 records · Page 3Linked to original sources

PubMed1995

Superficial esophageal carcinoma.

BACKGROUND: The detection of superficial esophageal carcinomas by surveillance endoscopy and the downstaging of advanced carcinomas to superficial carcinomas by induction therapy have increased the number of patients with these carcinomas undergoing resection. The natural history of these carcinomas is not well defined. METHODS: To evaluate the results of surgical resection and identify predictors of improved survival, a retrospective review of (1) patients with superficial esophageal carcinoma at presentation (SECP) and (2) patients with advanced carcinomas that were downstaged to no residual carcinoma or superficial esophageal carcinoma after induction therapy (SECD) was conducted. RESULTS: There were 54 patients with SECP (19 Tis and 35 T1). Survival was significantly better for patients with Tis carcinomas (85.3% at 5 years) and patients with intramucosal T1 carcinomas (79.4%) than for patients with submucosal T1 carcinomas (16.3%) (p = 0.007 and p = 0.045, respectively). Survival at 5 years for the 49 patients without regional lymph node metastases (N0) was 65.2%, whereas none of the 5 patients with regional lymph node metastases (N1) have survived more than 3 years (p = 0.054), and 3 died of recurrent disease. There were 21 patients with SECD (13 T0, 2 Tis, and 6 T1). Survival at 4 years was 58.2%. In this group, survival was not related to depth of tumor invasion (p = 0.76) or regional lymph node status (p = 0.68). CONCLUSIONS: We conclude that (1) patients with Tis and intramucosal T1 SECP have a significantly better survival than those with submucosal T1 SECP, (2) patients with N0 SECP have a significantly better survival than those with N1 SECP, and (3) survival of patients with SECD is not related to depth of tumor invasion or regional lymph node status.

Adenocarcinoma↗

PubMed1995

Palliative chemotherapy for non-small cell lung cancer.

The results of several randomized trials suggest a marginal survival benefit for patients with metastatic non-small cell lung cancer after treatment with chemotherapy. This intervention, however, has not become standard therapy. Toxicity, cost, and inconvenience have led many physicians to question whether chemotherapy has even a palliative role in this disease. Furthermore, it is well established that patients with a poor performance status, who are most in need of symptomatic palliation, are also those who are least likely to benefit and most likely to experience treatment-related toxicity. Nonetheless, evidence of a symptomatic benefit from combination chemotherapy has been presented. Indeed, symptomatic palliation can result even in the absence of a conventionally defined chemotherapy-induced response. Phase III trials supporting the palliative value of chemotherapy, however, have been limited and inconclusive. Fortunately, other palliative treatment modalities exist. These interventions should be carefully integrated with chemotherapy when an overall treatment plan appropriate for an individual patient is being developed. In addition to the symptomatic needs of each individual, this treatment plan must also address both physician and patient biases.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1994

Aggressive concurrent chemoradiotherapy and surgical resection for proximal esophageal squamous cell carcinoma.

BACKGROUND: Proximal esophageal cancer has been a disease associated with relatively poor treatment success, partly due to advanced disease at presentation and the morbidity of the surgery required. Therefore, most patients receive palliative radiation therapy, and disease control is poor. METHODS: Between July 1990 and December 1992, nine consecutive patients with proximal esophageal squamous cell carcinoma were treated with aggressive concurrent chemoradiotherapy followed by surgical resection. Treatment consisted of cisplatin (20 mg/m2/day) and 5-fluorouracil (1000 mg/m2/day), both given as continuous intravenous infusions over 4 days concurrent with accelerated fractionation external beam radiation therapy (150 cGy twice a day to a dose of 2400 cGy). Three weeks after beginning treatment, a second course of chemotherapy and accelerated fractionation radiation therapy was administered to a total preoperative radiation therapy dose of 4500 cGy. After restaging of their disease, patients next underwent surgical resection. A single postoperative course of chemotherapy and 2400 cGy of concurrent accelerated fractionation radiation therapy was administered to those patients with residual tumor in the resection specimen. Two of these nine patients also were given 4-day etoposide infusions (75 mg/m2/day) as part of their chemotherapy and received lower induction radiation therapy doses. RESULTS: Although significant toxicity was experienced, there were no deaths attributable to the chemoradiotherapy and only one perioperative death. All nine patients underwent surgery; five required pharyngolaryngoesophagectomy. No residual tumor was found in the resection specimen in three of the nine patients. Continuous locoregional tumor control was achieved in all patients. Only two developed distant metastases. CONCLUSIONS: These results, using aggressive multimodality treatment, suggest that excellent locoregional control and long term, disease free survival can be achieved in selected patients with proximal esophageal cancer.

Adult↗

PubMed1994

Aggressive multimodality therapy for malignant pleural mesothelioma.

Nineteen patients with clinical stage I malignant pleural mesothelioma were treated with aggressive multimodality therapy. Nine patients underwent pleurectomy and decortication followed by immediate intrapleural chemotherapy with cisplatin and mitomycin C. Ten patients required pleuropneumonectomy followed within 1 week to 2 weeks by intrapleural administration of cisplatin (100 mg). Four to 8 weeks after operation, 15 patients underwent postoperative adjuvant cisplatin-based systemic chemotherapy. There were three postoperative complications (16%) requiring reoperation and one postoperative death (5%). Intrapleural chemotherapy was well tolerated with no complications. Systemic chemotherapy was poorly tolerated, and there was one chemotherapy-related death. Sixteen patients (84%) experienced good to excellent palliation. Three patients are currently alive with no evidence of recurrent disease at 10, 35, and 43 months. The median overall survival was 13 months and the median disease-free survival, 11 months. Overall and disease-free 3-year survivals were 17% and 22%, respectively. Patients with epithelial malignant pleural mesothelioma had significantly better overall survival (p = 0.037) and disease-free survival (p = 0.02) than patients with sarcomatous or biphasic malignant pleural mesothelioma. We conclude that despite major toxicity, in select patients with clinical stage I malignant pleural mesothelioma, aggressive multimodality therapy offers effective palliation and occasional long-term disease-free survival.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1994

Adenocarcinoma of the esophagus and gastroesophageal junction. Clinical and pathologic assessment of response to induction chemotherapy.

A preoperative induction chemotherapy regimen consisting of two monthly courses of etoposide, doxorubicin, and cisplatin was given to 13 patients with nonmetastatic adenocarcinoma of the distal esophagus or gastroesophageal junction. Esophageal ultrasound examination was performed both before chemotherapy and again before surgery. Induction chemotherapy was poorly tolerated with 10 of the 13 patients experiencing at least one episode of severe neutropenia. Two of the 13 patients refused the second course of treatment. A symptomatic response to chemotherapy, defined as a reduction in the presenting symptom, was noted in 10 of the 13 patients (77%). Endoscopic improvement occurred in 9 of the 13 patients (69%). Esophageal ultrasound evidence of a reduction in either T or N stage was noted in only 2 of the 13 patients (15%), however, and neither of these responses was confirmed pathologically. Clinical evidence of disease progression was noted in 4 patients during chemotherapy. With a median follow-up of 31 months, the relapse-free and overall survivals are 25% and 31%, respectively. Despite significant toxicity, our chemotherapy regimen would be considered successful if assessed by symptomatic or esophagoscopic improvement. Esophageal ultrasound, careful pathologic staging, and our disappointing survival rates, however, suggest limited, if any, value for this approach.

Adenocarcinoma↗

PubMed1994

Continuous course radiation therapy and concurrent combination chemotherapy for squamous cell head and neck cancer.

Concurrent radiation therapy and chemotherapy is a promising approach to the treatment of squamous cell head and neck cancer. Toxicity, however, has required either scheduled breaks in radiation therapy administration or compromise in chemotherapy dose intensity. We describe the toxicity and results in 19 patients treated at diagnosis with a continuous course of radiation therapy and intensive concurrent combination chemotherapy using 5-fluorouracil and cisplatin. Toxicity among these 19 patients was significant, including mucositis, myelosuppression, and weight loss, and aggressive supportive efforts were required. No toxic deaths occurred, however. At the end of treatment, all patients had achieved complete control of their primary-site tumor. Primary-site resection was not required in any patient for tumor control, but neck dissections were performed in selected individuals with involved nodes at diagnosis. No patient recurred at the primary site and only a single patient recurred in the neck. We conclude that this chemoradiotherapy schedule is very effective, albeit toxic. Toxicity, however, can be managed with appropriate aggressive supportive measures. Confirmation of these encouraging treatment results will require performance of a randomized clinical trial.

Adult↗

PubMed1994

The community approach to salvage therapy for advanced head and neck cancer.

The natural history of squamous cell head and neck cancer is well understood. Locoregional approaches to salvage therapy for this disease have curative potential, primarily because distant metastases are uncommon. Before proceeding with salvage treatment, however, clinicians should identify the extent of disease and determine whether the treatment intent is curative or palliative. Because of the associated morbidity, surgery should be considered only in patients for whom cure of recurrent disease is feasible. Radiation therapy may be indicated in patients whose disease recurs after surgery and in selected patients in whom initial radiation has failed. Single-agent and combination chemotherapy, in particular the combination of cisplatin and 5-fluorouracil, has achieved overall response rates of 30% to 40% in patients with recurrent disease. However, cure after salvage chemotherapy has not been achieved. Until salvage treatment regimens capable of achieving significant long-term survival are identified, symptomatic palliation will remain the main treatment goal in this patient population.

Carcinoma, Squamous Cell↗

PubMed1993

Concurrent radiation therapy and chemotherapy for locally unresectable squamous cell head and neck cancer: an Eastern Cooperative Oncology Group pilot study.

PURPOSE: The feasibility and success of an intensive chemoradiotherapeutic protocol for patients with locally advanced, unresectable squamous cell head and neck cancer was tested in this limited-institution, Eastern Cooperative Oncology Group phase II pilot study. MATERIALS AND METHODS: Between December 1987 and September 1989, 57 patients were entered onto this trial. The treatment protocol consisted of three courses of a 4-day continuous fluorouracil infusion, a single cisplatin bolus injection, and concurrent split-course radiotherapy. After 30 Gy of radiation and two chemotherapy courses, patients were evaluated for response and for the possibility of surgical resection. RESULTS: Fifty-five of 57 registered patients are assessable for toxicity and 52 are assessable for response and survival. Toxicity was significant, but tolerable, although there were three toxic deaths. A complete response to this treatment was ultimately achieved by 77% of patients. Twenty-four patients remain relapse-free. The projected Kaplan-Meier 4-year relapse-free survival rate is 45% and the overall survival rate is 49%. Median relapse-free and overall survival durations are 26 and 37 months, respectively. Of the 28 treatment failures, 79% were locoregional. Fourteen patients underwent surgery. Six remain relapse-free. CONCLUSION: This aggressive concurrent chemoradiotherapy protocol appears feasible within a cooperative group. Treatment results are promising and appear durable. A randomized phase III clinical trial is currently underway.

Adult↗

PubMed1992

Concurrent radiation therapy, 5-fluorouracil, and cisplatin for stage II, III, and IV, node-negative, squamous cell head and neck cancer. Results and surgical implications.

METHODS: Between 1983 and 1989, 42 patients with Stage II, III, and IV, node-negative, squamous cell head and neck cancer were treated with concurrent 5-fluorouracil, cisplatin, and radiation therapy. Two courses of chemotherapy with 30 Gy of concurrent radiation therapy were to be followed in all patients by definitive surgery and then an additional 30 Gy of radiation therapy and one to two courses of chemotherapy. The patients who achieved a complete response to the initial induction treatment, however, did not undergo surgery. RESULTS: After the completion of all therapy, 41 of the 42 patients (98%) were considered disease-free. Only 4 of these 41 had relapses, for a projected Kaplan-Meier disease-free survival rate of 86%. Treatment failure occurred in no patients with Stage II, 1 of 17 patients with Stage III, and 4 of 14 patients with Stage IV disease. Of the 42 patients, 23 (55%) did not require surgery after achieving a complete response to induction therapy, and only 1 of these 23 patients subsequently had a relapse. CONCLUSIONS: Although the value of adding chemotherapy to conventional treatment remains unproven in squamous cell head and neck cancer, this treatment schedule appears promising in node-negative disease. Randomized trials will be necessary, however, to validate the efficacy of this approach and confirm the suggestion by the authors that surgery can be avoided in most patients with N0 disease.

Aged↗

PubMed1992

Esophageal carcinoma: esophageal ultrasound assessment of preoperative chemotherapy.

The effect of preoperative chemotherapy in the treatment of esophageal carcinoma is difficult to assess because of the inadequacies of clinical staging. Endoscopic esophageal ultrasound (EUS) has been shown to be accurate in the clinical determination of depth of tumor invasion (T) and regional lymph node status (N). Therefore, EUS may be useful in assessing the effect of preoperative chemotherapy in the treatment of esophageal carcinoma. Eleven patients with operable adenocarcinoma of the esophagus or esophagogastric junction underwent staging by EUS before treatment. This was followed by two courses (10 patients) or one course (1 patient) of chemotherapy: etoposide, 120 mg/m2 for 3 days; doxorubicin hydrochloride, 20 mg/m2; and cisplatin, 100 mg/m2. Restaging by EUS was done after treatment. Ten patients then underwent resection of the tumor with lymphadenectomy. One patient was found to have metastatic disease at thoracotomy and did not undergo resection. However, tissue sampling was adequate for the determination of pathological stage. Independent pathological determinations of T and N were then obtained. On completion of chemotherapy, 9 patients (82%) had relief or reduction of preoperative symptoms, and 9 patients (82%) had either no evidence of tumor or reduction of tumor size by endoscopy. Despite this clinical and endoscopic response, no patient had EUS-documented and pathology-confirmed reduction of T. However, 2 patients had EUS-documented and pathology-confirmed progression of N. The accuracy of EUS in the determination of T was 82% and of N, 73%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

PubMed1992

Adrenal carcinosarcoma presenting in a woman with clinical signs of virilization. A case report with immunohistochemical and ultrastructural findings.

An adrenal carcinosarcoma is reported in a 29-year-old female presenting with clinical signs of virilization. This is the first reported case of a functioning adrenal carcinosarcoma in the English language literature. The tumor measured 12.5 cm in greatest dimension, weighed 610 g, and consisted of large areas of typical adrenal cortical carcinoma that was, however, interspersed with multiple foci of sarcoma. Rhabdomyosarcomatous elements were identified and confirmed both immunohistochemically and ultrastructurally. After radical resection, the patient received adjuvant mitotane therapy but developed rapid local and metastatic recurrence. Systemic chemotherapy was unsuccessful, and the patient died 8 months after surgery.

Adrenal Cortex Neoplasms↗

PubMed1991

The use of recorded interviews to enhance physician-patient communication.

Audio recordings were made of the initial interview conducted between a cancer physician and 29 patients at the time of initial diagnosis and treatment planning. The tape recordings were then given to these patients to allow review as often as desired. Follow-up questionnaires were collected to evaluate this experience. We found that the recording session was well accepted and that the taped interviews were frequently reviewed, usually with family and friends. Despite the patients' initial feelings that both diagnosis and treatment plan were well understood, most felt that listening to the taped interview provided new information and a clearer understanding about their cancer care. The results of our study support the use of recorded interviews as a valuable tool to help patients and families cope with cancer and a successful method to improve communication with physicians.

Adult↗

PubMed1991

Diffuse well differentiated lymphocytic lymphoma: a clinical study of 22 patients.

An analysis is presented of the clinical and prognostic features of 22 patients diagnosed with diffuse well differentiated lymphocytic lymphoma at Cleveland Metropolitan General Hospital between 1974 and 1987. At presentation, the disease was usually advanced with 86% of patients having stage IV disease and 73% of patients exhibiting bone marrow involvement. Ten second malignancies were documented in 7 (32%) of our patients. The goal of treatment in our patients was palliation except in the 2 stage 1 patients. The response rate to initial treatment was 55% (15% complete), although 75% of patients ultimately responded to some form of therapy; and the mean survival was 58 months, a figure not different from historical controls. There were no differences in survival between patients given simple versus complex therapy at diagnosis or at any time during the course of their disease; and no differences in survival between complete, partial and nonresponders.

Adult↗

PubMed1990

Simultaneous versus sequential combined technique therapy for squamous cell head and neck cancer.

Forty-eight patients with locally confined (M0) squamous cell head and neck cancer were prospectively randomized to receive either simultaneous (SIM) or sequential (SEQ) combined technique therapy with a 5-fluorouracil infusion, a cisplatin bolus injection, and radiation therapy. Patients with residual resectable disease underwent surgery after induction therapy, whereas those achieving a complete response to induction did not require surgery. Patients on the two treatment arms were equivalent in all measured variables, including disease extent. Toxicities of the SIM and SEQ arms also were equivalent except for mucositis and the resultant weight loss, which were more severe on the SIM arm (P = 0.002). With a follow-up time ranging from 9 to 41 months, seven of the 24 SIM patients and 14 of the 24 SEQ patients are considered treatment failures. The relapse-free survival is significantly better on the SIM arm (P = 0.03), although an overall survival advantage has not yet been demonstrated (P = 0.13). The achievement of a complete response after induction therapy correlates with both the relapse-free (P = 0.0005) and overall (P = 0.05) survival, and the likelihood of an induction complete response also is significantly better for those treated with the SIM schedule (P = 0.02). Eighteen patients did not require surgery after achieving an induction complete response. Relapse-free survival does not appear to be compromised in this patient subset.

Adult↗

PubMed1990

Treatment of oral squamous cell carcinoma with simultaneous chemotherapy and radiation: results and surgical implications.

Thirty-seven patients with oral squamous cell carcinoma, many with advanced disease, were treated initially with a protocol using simultaneous intravenous 5-fluorouracil (5-FU) cis-platinum, and radiation. Twenty-two patients (62%) experienced complete remission after one cycle of therapy. Fifteen patients (38%) demonstrated an incomplete response; surgical resection was possible in 14 of these 15 patients. A second cycle of chemoradiotherapy was administered to all 37 patients. After this treatment resection is possible for some patients who are initially inoperable, and surgery is necessary only for those patients (38%) who show an incomplete remission after the first cycle of therapy and for those who present initially with bony invasion. Furthermore, the treatment of cervical nodes and intraoral disease may be divorced and the extent of surgery may be reduced for many patients. A 5-year survival of 76% is predicted for this group of patients. The described protocol shows promise for treatment of oral squamous cell carcinoma.

Adult↗

PubMed1990

Long-term results after chemoradiotherapy for locally confined squamous-cell head and neck cancer.

The long-term results after simultaneous chemoradiotherapy in 54 patients with previously untreated or minimally treated, locally confined (M0) squamous-cell carcinoma of the head and neck are presented. Multiple concurrent courses of radiation therapy and chemotherapy with cisplatin and a four-day 5-fluorouracil infusion were given. Twenty-eight patients underwent definitive surgery and 26 were treated without surgical resection. Treatment-associated toxicity was significant, including mucositis, myelosuppression, and a mean 12% loss of initial body weight. Of the 54 patients, 51 were ultimately rendered disease free by this combined modality protocol. With a follow-up ranging from 42-68 months, the projected Kaplan-Meier relapse-free survival for the entire patient cohort is 70%, with all relapses occurring within 17 months of patient entry. The projected Kaplan-Meier relapse-free survival for patients with Stage IV disease is 62%. The durability of these remissions suggests that there is a significant likelihood of cure in all patients with locally confined disease, and justifies comparative trials with standard treatment.

Adult↗

PubMed1989

Efficacy of high-dose oral leucovorin and 5-fluorouracil in advanced colorectal carcinoma. Plasma and tissue pharmacokinetics.

Thirty-one evaluable patients with advanced colorectal cancer were treated with oral leucovorin (LV) 500 mg/m2, administered hourly in four divided doses weekly for 6 weeks. Six patients received intravenous 5-FU at 450 mg/m2 and the remainder at 600 mg/m2 weekly for 6 weeks. This schedule was repeated after a 2-week rest period without medication. None of the patients had received previous chemotherapy. The results of the study showed a overall complete remission (CR) and partial remission (PR) of 45%. All responding patients received the 600-mg/m2 dose of 5-FU. There were five CR and nine PR. An additional seven (23%) patients had stable disease. Two of the seven received the 450-mg/m2 dose of 5-FU and the remainder received 600 mg/m2. The median disease-free interval for CR patients exceeded 25 months, while the interval for PR patients was 11.8 months. The median survival for CR patients was over 26.7 months and 16.5 months for the PR patients. The median survival for stable patients was 9.5 months and 5.5 months for patients with progressive disease. Toxicity included diarrhea in 70% of patients, excess lacrimal secretion in 35%, and nausea and vomiting in 25% There were no treatment-related deaths in this group. The authors conclude from this Phase I study that the optimal 5-FU dose in 600 mg/m2 combined with high-dose oral leucovorin for the treatment of advanced colorectal carcinoma.

Adenocarcinoma↗

PubMed1989

Long-term survival after chemoradiotherapy for locally advanced squamous cell carcinoma of the esophagus.

Seven patients with locally far-advanced, inoperable, squamous cell cancer of the esophagus were given two cycles of concurrent radiation and chemotherapy. Each cycle consisted of 5-fluorouracil 1,000 mg/m2/day given as a continuous intravenous infusion over 96 hours, cisplatin 75 mg/m2 given as an intravenous bolus on day 1, and methotrexate 40 mg/m2 given as an intravenous bolus on days 8 and 15. Three thousand rads of radiation were given in 15 fractions between days 1 and 19. Six patients are evaluable for response. Symptomatic relief was obtained by all six and was complete in 4. Five patients achieved a complete response, and two remain alive and disease free. Five of the six evaluable patients survived for at least 12 months. Aggressive chemoradiotherapy may result in significant survival prolongation and symptomatic palliation in this poor-prognosis subset of patients with esophageal cancer.

Adult↗