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Biomedical subjects

F A Shepherd

Publications and source records attributed to F A Shepherd.

At least 91 records · Page 5Linked to original sources
PubMed1992

Treatment of AIDS-related non-Hodgkin's lymphoma with a twelve week chemotherapy program.

Current treatment options for acquired-immunodeficiency syndrome (AIDS)-related non-Hodgkin's lymphoma (NHL) are unsatisfactory because of excessive toxicity rates and frequent recurrence of lymphoma. In this phase II study, we evaluated a novel 12 week chemotherapy program with respect to feasibility, toxicity and therapeutic results. Thirty HIV-seropositive patients with intermediate grade or small non-cleaved cell NHL received a 12 week program of weekly intravenous and oral chemotherapy consisting of etoposide, adriamycin, cyclophosphamide, bleomycin, vincristine, methotrexate and prednisone as well as biweekly intrathecal cytosine arabinoside. Prophylaxis against Pneumocystis carinii pneumonia (PCP) and candida were given routinely. The overall objective response rate was 73% with 33% complete responders. The time to progression for those stable or responding was 9.4 months. Five of 10 complete responders are well and free of disease 13.2 to 24.5 months from diagnosis. Median survival for the 30 patients was 8.1 months. NHL was the most common cause of death (13/22); opportunistic infection caused only one death (cryptococcal meningitis). Only 1 case of PCP occurred. The major toxicity was neutropenia. In conclusion this regimen resulted in response rates similar to other reports with acceptable toxicity and a very low incidence of PCP. Relapse of NHL remains a major challenge, however, and further studies are needed. Routine PCP prophylaxis should be incorporated into new trials of therapy for AIDS-related NHL.

AIDS-Related Opportunistic Infections↗
PubMed1992

Ifosfamide, cisplatin, and etoposide (ICE) in the treatment of advanced non-small cell lung cancer.

Forty-seven previously untreated patients with histologically or cytologically proven non-small cell lung cancer were treated with ICE (ifosfamide/cisplatin/etoposide). Patients received ifosfamide 4 g/m2 with mesna uroprotection on day 1, and cisplatin 25 mg/m2/d and etoposide 100 mg/m2/d on days 1, 2, and 3; courses were repeated every 28 days. Premedication with prochlorperazine, dexamethasone, and high-dose metoclopramide was given to prevent nausea; lorazepam was added on days 2 and 3 only. Thirty-four men and 13 women (median age, 60 years) received a total of 146 treatment cycles. One patient had stage IIIA disease, seven had IIIB disease, and 39 had hematogenous metastases. Forty-six patients were evaluable for response and toxicity. One patient suffered a myocardial infarction on day 7 that was judged unrelated to treatment. Two patients suffered early death from toxicity and have been classified as nonresponders. Three patients achieved complete response (median, 42+ weeks) and 14 patients achieved partial response (median, 29+ weeks; range, 10 to 82+), for an overall response rate of 37% (95% confidence limits, 23% to 51%). The median survival of the entire group is 26 weeks (1 to 82+). The median nadir granulocyte count was 0.275 x 10(9)/L (range, 0 to 2.3 x 10(9)/L), and there were 14 episodes (in 11 patients) or neutropenia-associated fever, one of which resulted in death. Seven of these patients had not had the required protocol dose reduction for nadir neutrophil count in the preceding cycle. The median nadir platelet count was 120 x 10(9)/L (range, 13 to 385 x 10(9)/L), and three patients required platelet transfusions. Eleven patients had RBC transfusions. Only ten patients had grade 2 gastrointestinal toxicity. Five patients had microscopic hematuria, and one patient had central nervous system toxicity.

Adult↗
PubMed1992

A phase II study of ifosfamide in combination with etoposide and cisplatin in the treatment of extensive small cell lung cancer.

The combination of etoposide and cisplatin has become one of the standard treatments for small cell lung cancer. Ifosfamide, an analogue of cyclophosphamide, has demonstrated single-agent antitumor activity comparable with that of the most active agents used to treat small cell lung cancer. Because ifosfamide is relatively nonmyelosuppressive and its principal dose-limiting toxicity, urotoxicity, has largely been eliminated with the introduction of the uroprotective agent mesna, we undertook a phase II study of the combination of all three agents (etoposide/ifosfamide/cisplatin) in good-performance-status, extensive-disease patients 70 years of age or younger. Twenty-five patients (17 men and eight women; median age, 58 years) were treated with 75 mg/m2 etoposide, 20 mg/m2 cisplatin, and 1.0 g/m2/d ifosfamide administered intravenously for 5 days. Mesna (200 mg/m2) was given as a bolus prior to the first day of chemotherapy and then daily by continuous infusion (900 mg/m2 over 24 hours) between administrations of chemotherapy. Mesna was continued for 12 hours after the last dose of ifosfamide. Treatment cycles were planned every 4 weeks for four cycles. Due to severe toxicities in the first eight patients, subsequent patients received only 4 days of treatment (20% dose reduction). Of the 25 extensive-disease patients studied, 23 are evaluable for response. Seven (30%) achieved a complete response and 10 (43%) had a partial response (overall response rate, 73%). Five patients (22%) had stable disease (< 50% decrease and no evidence of disease progression for at least 4 weeks), and disease progressed in 1 patient (4%). The median survival time was 42 weeks (range, 2 to 160+ weeks). Granulocytopenia was dose-limiting: median granulocyte count was 0.486 x 10(9)/L, 21% of cycles had a granulocyte nadir below 0.2 x 10(9)/L, and four patients died of sepsis. Three patients required platelet transfusion and nine needed blood transfusion. Microscopic hematuria occurred in eight patients (11% of treatment cycles) but was reversible in all cases. A number of central nervous system symptoms were reported but could not be definitely attributed to ifosfamide/mesna. Gastrointestinal toxicity was generally mild, which is attributed to the use of an aggressive antiemetic program. The etoposide/ifosfamide/cisplatin regimen is active and produced a complete response rate of 30% in extensive small cell lung cancer; the duration of response and survival appears similar to that of other standard regimens. The 5-day schedule produced excessive toxicity in this patient population, necessitating a 20% dose reduction (by using a 4-day schedule). The method of administration required a minimum of 5 hospital days per cycle.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1991

Dexamethasone/ifosfamide/cisplatin/etoposide (DICE) as therapy for patients with advanced refractory non-Hodgkin's lymphoma: preliminary report of a phase II study.

Twenty-two patients with refractory intermediate- or high-grade non-Hodgkin's lymphoma were treated with dexamethasone 10 mg every six hours and ifosfamide 1 g/m2, cisplatin 25 mg/m2, etoposide 100 mg/m2 (DICE), and mesna uroprotection daily x4 every 3 to 4 weeks. Pretreatment with prochlorperazine and metoclopramide was given to prevent nausea and vomiting. Eighteen men and four women, aged 21 to 74 years (median age, 65) have received a total of 64 cycles. Seventeen patients had stage IV, one had stage III, and four patients had stage II disease. Seven patients had B symptoms and 11 had marrow involvement. Only two patients had had more than one previous chemotherapy regimen. Median time from last chemotherapy to DICE was 7 months (range 1 to 41). Two patients who suffered early treatment-related deaths (from sepsis) were classified as nonresponders. Six of 22 patients (27%) achieved complete remission (2 to 22+ months), and 11 (50%) had partial remissions (1 to 8+ months) for an overall response rate of 77%. Median survival has not been reached yet, and 12 patients are alive 1 to 22 months from the start of treatment. Nine patients had nadir granulocyte counts less than 0.5 x 10(9)/L; six required RBC transfusions and five, platelet transfusions. The platelet nadir was less than 50 x 10(9)/L in 13 patients. Four patients had microscopic hematuria, two had grade 3 gastrointestinal toxicity, and one had a transient episode of delirium and blurred vision.

Adult↗
PubMed1991

The prognostic significance of pretreatment serum lactate dehydrogenase in patients with small-cell lung cancer.

Pretreatment serum lactate dehydrogenase (LDH) levels were assayed in 288 patients presenting with small-cell lung cancer (SCLC) between 1976 and 1985. Patients were routinely staged by physical examination, chest x-ray, bone, brain, and liver scans, and bone marrow evaluation. Clinical response and survival were assessed following treatment with combination chemotherapy as part of four clinical trials. Patients with extensive disease (ED) presented with a higher incidence (108 of 147, 73%) of abnormally elevated LDH (greater than 193 IU/L) than those (65 of 141, 46%) with limited disease (LD) (P = 2 x 10(-6)). Forty percent of patients had an initial normal LDH level and a higher response rate (89 of 108, 82%; complete response [CR], 47%) than those with elevated values of LDH (119 of 156, 76%; CR, 29%). The CR rate varied inversely with the level of LDH in patients with LD (P = .026) but not in those with ED (P = .300). The median survival time and 1-year and 2-year survival rates for patients with elevated LDH were 39 weeks and 33% and 6%, respectively, whereas for those with a normal LDH level these were 53 weeks and 54% and 16%, respectively. Patients with LD and elevated levels of LDH manifested a higher relative death rate (1.63:1) when compared with patients with LD and LDH in the normal range (P = .0083). The survival of patients with ED did not differ between those with normal and elevated levels of LDH (P = .273). A significant survival advantage persisted for patients with LDH in the normal range following adjustments for extent of disease, performance status (PS), and treatment protocol (P = .044, log-rank analysis). In conclusion, serum LDH appears to be a significant independent pretreatment prognostic factor in patients with SCLC that correlates with stage of disease, response to treatment, and survival.

Adult↗
PubMed1991

Small-cell carcinoma of the lung: derivation of a prognostic staging system.

Retrospective data on 22 pretreatment attributes were evaluated in 614 patients with small-cell carcinoma of the lung (SCCL). The series included 284 patients with limited disease (LD) and 328 patients with extensive disease (ED) managed between 1974 and 1986. Prognostic factors were evaluated by univariate analysis and by the Cox multivariate regression model. Recursive partition and amalgamation algorithm (RECPAM), two clustering methods well suited for obtaining strata and adapted for censoring survival data, were developed and used in the formulation of a new prognostic staging system. In univariate analysis, prognosis was significantly influenced by extent of disease (DE), the number of metastatic sites, and the detection of mediastinal spread in LD. Poor performance status (PS), male sex, and advanced age were negatively correlated with survival, as were increased serum levels of alkaline phosphates (AP), lactate dehydrogenase (LDH), carcinoembryonic antigen (CEA), total WBC count (WBCC), and low platelet count and low serum sodium. The Cox model identified plasma LDH and mediastinal spread as the only significant factors in LD; the influence of PS, number of metastatic sites, bone metastasis, brain metastasis, and platelet count were identified as significant in ED. The RECPAM model identified four distinct risk groups defined in a classification tree by the following eight attributes: DE, PS, serum AP, serum LDH, mediastinal spread, sex, WBCC, and liver metastasis. The four groups were distinguished by median survival times of 59, 49, 35, and 24 weeks, respectively (P = .0001). Interactions among prognostic factors are emphasized in the RECPAM classification model as evidenced by reassignment of patients across conventional staging barriers into alternate prognostic groups. The advantages of using RECPAM over the more conventional Cox regression techniques for a new staging system are discussed.

Adult↗
PubMed1991

Is there ever a role for salvage operations in limited small-cell lung cancer?

Combined modality treatment with chemotherapy and radiation produces tumor regression in most patients with small-cell lung cancer, but the impact on survival has been small, and less than 20% of patients with limited disease survive 2 years. Survival time is extremely short after failure to respond or relapse after treatment. Local control remains a problem, with one third of patients having recurrence only at the primary site. In an attempt to prolong survival and perhaps achieve cure, we undertook surgical resection in 28 patients with limited small-cell lung cancer who did not have complete remission with standard treatment or who had only local recurrence after treatment. There were 28 patients, 22 male and six female, median age 61 years (range 41 to 76). All patients had been treated with chemotherapy and 13 had received preoperative radiotherapy to the primary site and mediastinum. Eight patients underwent an operation for relapse after complete remission. Five patients had had no response to treatment, three had had a slight response followed by progression during chemotherapy, and 12 had achieved partial response but had greater than 3 cm residual masses. Twelve patients required pneumonectomy, 15 lobectomy, one patient had unresectable disease, and two had bulky residual masses after the operation. Three others had microscopic residual disease. Pathologic examination showed only small-cell lung cancer in 18 patients, mixed small-cell and non-small-cell in four, and only non-small-cell lung cancer in six. There were only four patients with stage I disease, 10 with stage II, and 14 with stage III. The median survival from the date of diagnosis for the entire group is 105 weeks and from the date of operation, 74 weeks. The projected 5-year survival rate is 23%. The two patients with residual masses died with local progression, and distant metastatic disease developed in 17 others. One patient died at 6 years without recurrent disease. Eight patients are alive 2 to 5 years after diagnosis. Seven of these patients required only a lobectomy, four had stage I disease, two had stage II, and two had stage III disease. Five had pure small-cell lung cancer and three had mixed small-cell and non-small-cell tumors. All of the patients with pathologic stage I disease remain alive compared with one of 10 with stage II disease and two of 14 with stage III. In summary, relapse or failure to respond to chemotherapy may be due to non-small-cell lung cancer or a mixed tumor.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1991

Surgical treatment for limited small-cell lung cancer. The University of Toronto Lung Oncology Group experience.

Since 1977, 119 patients with limited small-cell lung cancer have undergone combined modality therapy including surgery at our institution. Seventy-nine patients (58 male, 21 female; median age 63 years) had surgery first, and 67 of these had adjuvant chemotherapy. Forty (27 male, 13 female; median age 59 years) had chemotherapy first, and 94% had a complete or partial response before the operation. Pretreatment staging revealed 69 stage I, 27 stage II, and 23 stage III tumors. Twenty-six patients required pneumonectomy, 88 lobectomy, and five had no resection. Four patients had gross and six had microscopic residual disease. Postoperative pathologic examination showed small-cell lung cancer only (n = 95), non-small-cell lung cancer (n = 3), mixed (n = 17), and no residual tumor (n = 4). Postoperative staging revealed 35 stage I, 36 stage II, and 48 stage IIIa tumors. The median survival of the entire group is 111 weeks and the projected 5-year survival rate is 39%. No survival difference was seen between patients treated with chemotherapy before the operation and those undergoing an initial operation followed by chemotherapy (p = 0.756). The median survival for patients with pathologic stage I disease has not been reached, and the projected 5-year survival rate is 51%. This is significantly better than for the patients with stage II (median 82 weeks, p = 0.001) or stage III (median 83 weeks, p = 0.001) disease, who have projected 5-year survival rates of 28% and 19%, respectively. Seven of the 12 patients who had no adjuvant chemotherapy remain alive at 6 to 48+ months. Sixty-seven patients have died (11 had no evidence of disease). Only 10 patients had a relapse in the primary site alone, seven at the primary and distant sites, and 39 only in distant sites. In summary, resection improves control at the primary site, and a significant proportion of patients with stage I (N0) disease achieve long-term survival and cure with combined modality therapy including surgery. Stage II and IIIa patients have survival predictions similar to stage IIIa non-small-cell lung carcinoma treated surgically.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Prospective assessment of cardiac function in patients with Kaposi's sarcoma and the acquired immune deficiency syndrome.

Prospective evaluation of cardiac function was undertaken in 21 patients with Kaposi's sarcoma (KS) and the acquired immune deficiency syndrome (AIDS) as part of a phase II clinical trial of 4'epirubicin. All patients were homosexual or bisexual males of median age 34 years (range 23-65). All patients had disseminated cutaneous involvement by KS and seven had systemic organ involvement. No patient had a history of cardiac symptoms, and physical examination of the cardiovascular system was within normal limits for all patients. The baseline ECG was normal in only nine patients (45%). Five had non-specific S-T segment and T-wave changes. Two had poor R-wave progression, and one patient each had incomplete right bundle branch block, left axis deviation, and voltage criteria suggestive of left ventricular hypertrophy. Radionuclide angiography was performed on all patients and compared to 12 age-matched, low-likelihood male controls. The mean ejection fraction (EF) at rest was 61.0 +/- 8.4%, and was not significantly different from the normal control value of 62.4 +/- 7.0%. Similarly the EF during exercise was 66.7 +/- 5.0%, again not significantly different from the control value of 67.8 +/- 5.8%. A drop in EF during exercise was seen in five of 15 KS patients compared to three of 12 controls. Chamber size was normal for both ventricles in only 14 patients (67%) with right ventricular dilatation seen in seven patients (33%). Wall motion abnormalities were also seen in nine patients (42.9%), with the right ventricle affected in eight patients (38.1%), chiefly involving the apex. No chamber size or wall motion abnormalities were seen in the control patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1991

Comparison of three HIV antigen detection kits in sequential sera from a cohort of homosexual men.

HIV antigen detection kits are available from a number of commercial sources. Abbott, Coulter, and Du Pont antigen kits were used to test 661 sera collected sequentially from 65 members of the Toronto Sexual Contact Study (TSCS). The sera had been collected at 3-month intervals over 4 years from nine persistently HIV-seronegative men, 14 seroconverters, and 42 seroprevalent participants. Antigen was not detected in any seronegative men. Two of 14 seroconverters were antigen positive in the specimen immediately preceding seroconversion (by all kits). Antigen was detected in 22 of 56 seropositive participants; of these, 16 of 22 demonstrated the emergence of antigen during observation. Discrepancies were noted in the time of detection of antigen (ranging from 3 months to more than 3 years) in nine participants. Although overall concordance among all kits for all specimens appears high (95.4%), when the bias introduced by testing multiple specimens from the same patient is removed, the lower bound of concordance among all three kits is estimated to be 80%. Similarly, after correction, the upper and lower bound of estimates of sensitivity are Abbott 96, 92%; Coulter 88, 63%; and Du Pont 88, 58%. There are significant differences in the performance characteristics of these commercial products for the detection of HIV antigen in serum.

AIDS-Related Complex↗
PubMed1990

Cofactors of progression to acquired immunodeficiency syndrome in a cohort of male sexual contacts of men with human immunodeficiency virus disease.

In a cohort of 249 male sexual contacts of men with acquired immunodeficiency syndrome (AIDS) or an AIDS-related condition in Toronto, Ontario, Canada, 143 cohort members were seropositive on enrollment and 16 seroconverted between initial recruitment in July 1984 to July 1985 and December 1988. Data on age, smoking and drinking status, recreational drug use, and history of sexually transmitted diseases and other diseases were obtained from interviews at induction and during follow-up on the cohort members every 3 months. Cox relative risk regression models, in which time was calculated from estimated date of human immunodeficiency virus (HIV) infection for seroprevalent cohort members and from 90 days prior to the first positive test for seroconverters, examined the potential effect of use of a variety of recreational drugs and the occurrence of selected infections on the risk of development of AIDS. Thirty-five cohort members developed AIDS while under study. No significant association with risk of progression to AIDS was noted for use of various recreational drugs (singly or in combination), history of specific infections, age at enrollment, or smoking and drinking status at enrollment. Only estimated duration of HIV infection appeared to be associated with increasing risk of development of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Late neurological complications after prophylactic cranial irradiation in patients with small-cell lung cancer: the Toronto experience.

We retrospectively analyzed the charts of 58 long-term survivors of small-cell lung cancer (SCLC) (greater than 2 years) for neurological complications and their impact on the well-being of these patients. We also attempted to have patients complete a questionnaire regarding any possible neurological problems. This was done in 14 patients. Metastasis to the CNS occurred significantly less often in patients who received prophylactic cranial irradiation (PCI) in a dose of 20 Gy in five equal fractions (two of 48), compared with patients who did not receive it (four of 10) (P less than .006). Delayed neurological complications occurred in nine of 48 (19%) patients who received PCI. However, in only two patients did PCI appear to be responsible for progressive dementia. In the other seven patients (one with weakness in the arms and legs, one with transient left hemiparesis, two with hearing loss, and three with various visual disturbances), chemotherapeutic agents (mainly cisplatin and vincristine) and underlying diseases probably contributed significantly to the occurrence of these complications. In addition, these neurological disturbances were transient or ran a stable course and did not adversely affect the daily life of these patients. In comparison, amongst the 10 patients who did not receive PCI one had progressive dementia and another had hemiparesis secondary to probable brain embolism. We conclude that the use of PCI in these doses was effective in reducing the frequency of CNS metastases and had an adverse effect on the daily life and well-being only in a minority of the patients. Until results of controlled randomized studies show otherwise, PCI should continue to be used as a part of the combined modality treatment of completely responding patients with limited SCLC.

Aged↗
PubMed1990

Phase II study of amonafide: results of treatment and lessons learned from the study of an investigational agent in previously untreated patients with extensive small-cell lung cancer.

Thirteen previously untreated patients with extensive small-cell lung cancer (SCLC) were treated with the investigational agent amonafide in a dose of 300 mg/m2 intravenously (IV) over 1 hour daily for 5 consecutive days. No responses were seen in 12 eligible patients. Myelosuppression was only occasionally seen. Other toxicities included diaphoresis, chest pain, local irritation at the injection site, arthralgias, nausea and vomiting, and neuromuscular problems. There were two early deaths, both attributable to tumor progression with resultant obstruction of a vital structure. Ten patients crossed over to alternate active therapy (etoposide [VP-16]-cisplatin) and five responded. The median survival time (MST) of the whole group of treated patients was 31 weeks. In future trials of investigational new drugs in previously untreated SCLC, we recommend that patients with the following characteristics be excluded: Eastern Cooperative Oncology Group (ECOG) performance status 2, 3, and 4; superior vena cava (SVC) obstruction; any major paraneoplastic syndrome; serious comorbid illness; and extensive hepatic involvement by tumor. The trial design should include prompt crossover to active alternative therapy, such as VP-16 and cisplatin, for disease progression or for failure to respond after two treatment cycles. Also, the trial design should use an early stopping rule based on interest in identifying only very active agents with a minimum response rate of 30%.

Adenine↗
PubMed1990

5-Fluorouracil with folinic acid is not effective against metastatic adenocarcinoma of the lung.

Thirty patients with a diagnosis of metastatic adenocarcinoma of the lung were entered on a trial to evaluate the antitumor efficacy of 5-fluorouracil 370 mg/m2 daily for 5 days every four weeks in combination with folinic acid 200 mg/m2, 60 min prior to 5FU. All patients had a good performance status, bidimensionally measurable disease, and weight loss less than or equal to 5% of preillness weight. Of the 29 evaluable patients, only two (7%) had partial responses (95% confidence limits 1-24%). Eleven (38%) had stable disease and 16 (55%) progressed. The two responding patients survived 12 and 60+ weeks. The median survival of all evaluable patients was 25 weeks (range 7-60+) and that of the stable patients was 26 weeks. The principal toxicities observed were diarrhea and stomatitis. Myelosuppression was rarely dose limiting. In contrast to the results of treatment with 5FU and folinic acid in metastatic colorectal cancer and breast cancer, the results of treatment with this combination of agents have been much less encouraging in adenocarcinoma of the lung.

Adenocarcinoma↗
PubMed1990

A phase II study of ifosfamide, cisplatin, etoposide in patients with advanced non-small cell lung cancer: a preliminary report.

Twenty previously untreated patients with histologically or cytologically proven non-small cell lung cancer (NSCLC) were treated with ifosfamide in combination with cisplatin and etoposide. Patients received ifosfamide 4 g/m2 with mesna uroprotection on day 1 and cisplatin 25 mg/m2 and etoposide 100 mg/m2 on days 1 through 3. Courses were repeated every 28 days. Premedication with prochlorperazine, dexamethasone, and high-dose metoclopramide was given to prevent nausea, and lorazepam was added on days 2 and 3 only. Seventeen male and three female patients (median age, 57 years) have been treated. Two patients had stage IIIb disease, and 18 had hematogenous metastases. Eighteen patients are evaluable for response and toxicity, and it is too early to evaluate two patients. Early in the study, two patients died of toxicity and have been classified as nonresponders. One patient achieved complete response (21+ weeks), and seven patients achieved partial response (median, 30+ weeks; range, 5 to 38+), for an overall response rate of 44.5%. The median survival of the group has not been reached, and 14 patients are alive 5 to 38+ weeks from the start of treatment. The median nadir granulocyte count was 0.275 x 10(9)/L (range, 0 to 2.283 x 10(9)/L), and there were six episodes (involving 5 patients) of neutropenia-associated fever, one of which resulted in death. The median nadir platelet count was 120 x 10(9)/L (range, 13 to 385 x 10(9)/L), but no patient experienced bleeding or required platelet transfusions. Five patients required RBC transfusions. Only eight patients had grade 2 gastrointestinal toxicity, and one patient had microscopic hematuria; there was no CNS toxicity.

Adult↗
PubMed1989

Hepatocellular carcinoma: pilot trial of treatment with Y-90 microspheres.

The potential use of yttrium-90 glass microspheres in the treatment of hepatocellular carcinoma was assessed in a pilot study of seven patients. The Y-90 microspheres were injected via a hepatic artery catheter. In this group of patients, no toxicity was observed for absorbed doses of between 5,000 and 10,000 cGy to the liver and up to 32,000 cGy to the tumor itself. Tumor response was seen only at the higher absorbed doses. The new Y-90 glass microspheres can safely deliver large doses of internal radiation to hepatic tumors as long as extrahepatic shunting can be excluded. Extrahepatic shunting will be the main limitation to this form of radiation therapy.

Brachytherapy↗
PubMed1989

Carcinoembryonic antigen, arginine vasopressin and calcitonin as markers of early small-cell lung cancer relapse.

Patients with small-cell lung cancer (SCLC) underwent serial blood monitoring during remission: 66 were tested for carcinoembryonic antigen (CEA) and calcitonin (CTN), including 40 who were concomitantly tested for arginine vasopression (AVP) as well. 83% of the patients had at least one assay elevated prior to induction therapy. By serial monitoring, blood concentrations reflected disease course and reached lowest levels at remission. CEA, AVP and CTN shifted along the course of disease independently of each other; a normal pretreatment titer did not preclude its rise at a later phase, while an initially elevated assay could normalize at remission and stay normal thereafter. The median lead time (LT) to clinically diagnosed relapse, for limited-disease patients, was 229 days for complete and 90 days for partial remitters. Patients with extensive disease had similar LT values. LT to local recurrence was shorter than to distant relapse. Remission AVP titers of up to 6 ng/ml conferred disease-free survival (DFS) longer than that associated with higher titers (median DFS 518 vs. 211 days, respectively; p = 0.045 for curve differences). The relative risk (RR) of relapse associated with pretreatment patient characteristics and with absence or presence of tumor marker normalization at remission was estimated by the Cox proportional hazards model. This analysis revealed that the RR of relapse conferred by pretreatment attributes, e.g. disease extent, was considerably modified by biochemical co-variates at remission, e.g. serum CEA level relative to a 3 ng/ml cutoff point.

Arginine Vasopressin↗