Additional Systemic Therapy Research Articles

Prognosis and survival outcomes in melanoma patients with unknown primary site (MUP)

7544 Background: Metastatic melanoma in lymph nodes (LN) in the absence of a known primary site (MUP) can be accurately diagnosed with current histologic methods. However, the true incidence, stage, prognostic factors, treatment, and long-term outcomes of this clinical entity are poorly defined. Methods: A retrospective analysis was performed of 820 consecutive melanoma patients diagnosed between 1990 and 2001 at a tertiary cancer center with melanoma metastatic to regional LN. Of these, 71 patients (8.7%) were confirmed to have MUP without distant metastatic disease. Clinicopathologic and treatment factors were analyzed to determine their impact on long-term disease-free outcome. Results: The most common presentation was a palpable mass in the axillary nodal basin (76%) in a male patient (72%) with a median age of 51 years. Following completion LN dissection (average 22 LN removed), AJCC 2002 (N) category was identified as N1, N2 or N3 in 34 (46%), 11 (16%) and 26 (38%) patients, respectively. Forty-three patients (61%) received additional systemic therapy and 17 patients (24%) were treated with postoperative adjuvant radiotherapy (XRT). With a median follow-up of 7.6 years, the overall 5- and 10-year disease-free survival rates were 53% and 41%, respectively. Five-year regional control was accomplished in 82% of patients. The median times to distant failure and death were 3.03 and 6.05 years, respectively. Male gender and N3 disease were significant predictors of disease-free survival by univariate analysis, while multivariable analysis revealed that gender was the only significant negative prognostic factor. Conclusions: MUP is not an uncommon clinical entity. The relatively favorable long-term survival of these patients supports the premise that MUP with nodal disease represents a manifestation of stage III melanoma rather than stage IV (M1a) subcutaneous/distant nodal disease. Therefore, patients with MUP should be treated with aggressive surgical approaches with curative intent and also be offered participation in adjuvant therapy protocols. No significant financial relationships to disclose.

CDH1 and CDH13 methylation in serum is an independent prognostic marker in cervical cancer patients.

Cervical cancer is the principal cause of death due to cancer in women. Five-year survival rate ranges from 15-80%, depending on the extent of the disease. New predictive markers for relapse may increase survival rates by improving treatment of patients at high risk for relapse. The gene products of CDH1 and CDH13, namely E-cadherin and H-cadherin, play a key role in cell-cell adhesion. Inactivation of the cadherin-mediated cell adhesion system, caused by aberrant methylation, is a common finding in human cancers. To test the hypothesis that CDH1/CDH13 methylation is a prognostic marker in cervical cancer we determined the methylation status of CDH1/CDH13 in serum samples from 93 cervical cancer patients. Methylation analysis was carried out using MethyLight. Aberrant methylation of the 5'-region of CDH1 or CDH13 was observed in 43% (40 of 93) of the patients. Cervical cancer patients with unmethylated CDH1/CDH13 in serum samples showed significantly better disease-free survival in univariate and multivariate analysis. Median disease-free survival for CDH1/CDH13 methylation negative and positive patients was 4.3 years and 1.2 years, respectively. Our results suggest that detection of aberrant methylation of CDH1/CDH13 may be of potential use as a marker for selecting cervical cancer patients at high risk for relapse who could benefit from additional systemic therapy.

Maintaining treatment of locally advanced breast cancer

Locally advanced breast cancer is a specific clinic entity, comprising various degrees of breast cancer local and regional extension. This term is applied to nonmetastatic large primary tumors (including inflammatory breast carcinoma), with or without extensive regional lymph node involvement, with a rapid or slow evolution, and usually with poor prognosis. This clinical presentation of mammary carcinoma is common in developing countries (30% to 60%), but also with a remarkable incidence in developed countries (10% to 20%). During many decades patients were treated with radical surgery or radiation therapy and with their combination, but always with poor results. The inclusion of neoadjuvant chemotherapy in the treatment enabled more favorable treatment results. The mortality from disseminated disease is the main problem in these patients, inducing the question of need for additional postoperative adjuvant systemic therapy. For steroid receptor positive patients hormonotherapy is a convenient choice of maintaining treatment. In endocrine non-responsive tumors, the role of postoperative chemotherapy is doubtful, having in mind preoperative chemotherapy and cumulative toxic effects. New trials including the large number of patients are necessary to obtain the definite answer whether the maintaining chemotherapy is useful but today it seems that additive postoperative treatment is not more efficient than preoperative alone.

Local antibiotic therapy guided by microbiological diagnosis.

The aim of this study was to determine the distribution patterns of Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans in periodontitis patients after standard mechanical periodontal therapy, and to evaluate the effect of additional local antibiotic therapy, given to all teeth with cultural evidence of these bacteria. 17 patients were included. 852 separate subgingival microbial samples were taken from the mesial and distal aspect of every tooth in 17 subjects at baseline. 46 of these samples, from 10 positive subjects, showed cultural evidence for P. gingivalis. 82 samples, from 5 subjects, were A. actinomycetemcomitans-positive. Three subjects showed no evidence for persistence of A. actinomycetemcomitans or P. gingivalis. In the other 14 subjects, all A. actinomycetemcomitans- or P. gingivalis-positive teeth were treated with tetracycline fibers (ACTISITE(R)). Sub-gingival microbial samples were again taken from two sites of every tooth, 1 month after fiber removal. 89% of the initially P. gingivalis-positive sites were now negative, but 16 previously negative sites now tested positive. 77% of the initially A. actinomycetemcomitans-positive sites were now negative, but 5 previously negative sites now tested positive. The teeth with persisting P. gingivalis or A. actinomycetemcomitans were again treated with fibers. Two sites of every tooth were once more sampled after 1 month. At this time, 5 subjects still showed cultural evidence of P. gingivalis at a total of 19 sites, and 4 subjects were positive for A. actinomycetemcomitans in a total of 27 sites. These 9 patients were finally submitted to systemic antibiotic therapy (3 x 250 mg metronidazole plus 3 x 375 mg amoxicillin/d for 7 days). Despite of all efforts, P. gingivalis was again detected 3 months later in isolated sites in 3 subjects, and A. actinomycetemcomitans could be cultivated from one single site. Therapy with tetracycline fibers guided by microbiological diagnosis effectively reduced P. gingivalis and A. actinomycetemcomitans locally, but was unable to completely eradicate the target organisms. Additional systemic antibiotic therapy further reduced P. gingivalis and A. actinomycetemcomitans. The observed persistence patterns suggest that reemergence of A. actinomycetemcomitans was due to recolonization, whereas the strikingly reproducible local reemergence of P. gingivalis in some sites indicated failed eradication.

Asthma refractory to glucocorticoids: the role of newer immunosuppressants.

Asthma is orchestrated by cytokine products of activated T cells. Glucocorticoids are thought to ameliorate asthma at least partly through T cell inhibition. Consequently, other T cell immunomodulatory agents have been assessed for asthma therapy. Since these agents may have serious unwanted effects, attention has been focused on patients with severe asthma refractory to maximal topical, and additional systemic glucocorticoid therapy. Although gold salts show a modest but significant glucocorticoid-sparing effect in severe asthma, lung function is not improved and not all patients respond. The minimum duration of a valid trial of therapy is probably 6 months. Unwanted effects include dermatitis, hepatic dysfunction, proteinuria and interstitial pneumonitis. Meta-analysis of trials of methotrexate in oral glucocorticoid-dependent asthma have confirmed that concomitant weekly methotrexate for a minimum of 3 to 6 months enables significant (approximately 20%) overall reduction in oral glucocorticoid requirements, although only approximately 60% of patients show a significant response. There is little effect on lung function. Blood count and liver function must be monitored. Opportunistic infection is rare but potentially fatal. Cyclosporine, administered for at least 3 months, is effective in only a proportion of patients with oral glucocorticoid-dependent asthma, where it may improve disease severity and/or enable oral glucocorticoid dosage reductions. Regular monitoring of renal function, blood pressure and blood concentrations of cyclosporine is required. The evidence that intravenous immunoglobulin (Ig) is of any benefit in patients with glucocorticoid-dependent asthma is at present equivocal. The therapy is expensive and associated with a high incidence of unwanted effects (fever, aseptic meningitis, urticaria). The macrolides tacrolimus (FK506) and sirolimus (rapamycin) have end effects similar to those of cyclosporine. Brequinar sodium, mycophenolate mofetil and leflunomide are inhibitors of de novo synthesis of pyrimidines and purines, to which T cells are particularly sensitive. Such drugs may in theory be beneficial for therapy of patients with oral glucocorticoid-dependent asthma. Humanized anti-CD4, anti-IgE and anti-interleukin (IL)-5 monoclonal antibodies, and other cytokine inhibitors such as soluble IL-4 receptor have entered early trials. The worth of current immunomodulatory drugs is limited since: (i) not all patients respond, and response cannot be predicted a priori; (ii) the high incidence of unwanted effects makes it difficult to assess overall benefit/risk ratios; (iii) there is increased risk of opportunistic infection and (theoretically) neoplasia; (iv) there are many relative and absolute contraindications to therapy; and (v) there is lack of knowledge about the long-term effects, beneficial or otherwise, of therapy.

COCCIDIOIDOMYCOSIS PRESENTING AS TESTICULAR MASS

No AccessJournal of UrologyCLINICAL UROLOGY: Case Reports1 Oct 2001COCCIDIOIDOMYCOSIS PRESENTING AS TESTICULAR MASS JOSEPH C. LIAO and ROBERT E. REITER JOSEPH C. LIAOJOSEPH C. LIAO More articles by this author and ROBERT E. REITERROBERT E. REITER More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(05)65785-0AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "COCCIDIOIDOMYCOSIS PRESENTING AS TESTICULAR MASS." The Journal of Urology, 166(4), p. 1396 References 1 : Fungal infections of the genitourinary system: manifestations, diagnosis, and treatment. Urol Clin North Am1999; 26: 701. Google Scholar 2 : Genitourinary coccidioidomycosis. J Urol1988; 140: 370. Link, Google Scholar 3 : Genitourinary aspects of disseminated coccidioidomycosis. J Urol1975; 113: 82. Link, Google Scholar From the Department of Urology, University California Los Angeles School of Medicine, Los Angeles, California© 2001 by American Urological Association, Inc.FiguresReferencesRelatedDetails Volume 166Issue 4October 2001Page: 1396 Advertisement Copyright & Permissions© 2001 by American Urological Association, Inc.KeywordscoccidioidomycosisabnormalitiestestisMetricsAuthor Information JOSEPH C. LIAO More articles by this author ROBERT E. REITER More articles by this author Expand All Advertisement PDF downloadLoading ...

Treatment of Cows with Retained Fetal Membranes with Ceftiofur

Retention of fetal membranes occurs after 5 to 15% of calvings. One of the most common treatments is the manual removal of the retained membranes and a local antibiotic treatment. An additional systemic therapy with antibiotic drugs is recommended for cows with a body temperature ~39.5°C. (103.1 °F). However, efficiency of manual removal and local antibiotic treatment is under discussion. The objective of this study was to compare this common treatment of retained fetal membranes to a protocol without manual removal or local intrauterine administration of antiobiotics, but use of ceftiofur as a systemic antibiotic treatment in case of elevated temperature.

Improved survival after one course of perioperative chemotherapy in early breast cancer patients: long-term results from the European Organization for Research and Treatment of Cancer (EORTC) Trial 10854

The aim of this study was to examine whether one course of perioperative polychemotherapy yields better results in terms of survival, progression-free survival (PFS) and locoregional control than surgery alone in early stage breast cancer. From 1986 to 1991, 2795 patients with stage I/II breast cancer were randomised to receive either one perioperative course of an anthracycline-containing chemotherapeutic regimen within 36 h after surgery or surgery alone. Patients were followed-up for overall survival, PFS and locoregional recurrence. The median follow-up period at time of the analysis was 11 years. PFS and locoregional control were significantly better (P=0.025 and P=0.004, respectively) in the perioperative chemotherapy arm. Node-negative patients seemed to benefit most from the perioperative FAC. Patients who received perioperative chemotherapy and locoregional therapy alone had significantly better overall survival rates than patients who received locoregional therapy alone (P=0.004). Patients who received additional systemic therapy did not seem to benefit from one course of perioperative chemotherapy (P=0.65). One course of perioperative polychemotherapy does improve PFS and locoregional control in early stage breast cancers. This effect is still present after 11 years of follow-up.

Herpes zoster in breast cancer patients after radiotherapy.

We have studied the incidence of herpes zoster in patients with adjuvant radiotherapy for breast cancer with special emphasis on possible correlations with other prognostic factors or survival. From 1/1985 through 12/1993, 1,155 breast cancer patients received postoperative radiotherapy with curative intent in our department. After mastectomy 961 patients were irradiated and after breast-preserving treatment 194 patients. The age ranged from 34 to 79 years, the median follow-up was 3.1 years (range: 0.3 to 12.4 years). There were 443 women (38%) pre- and 712 (62%) postmenopausal. 21% had T3- to T4-tumors, 55% had axillary lymph node involvement, and 65% received additional systemic hormonal and/or cytotoxic therapy. In case of postmastectomy radiotherapy, the lateral chest wall and lymphatics (axilla, parasternal and supraclavicular nodes) were irradiated with an anterior photon field to 50 Gy (axilla 44 Gy) and most of the chest wall with an electron field to 44 Gy in 2-Gy fractions. After breast-preservation, the breast was irradiated via tangential fields with 6- to 8-MV photons up to 50 Gy plus 8 Gy electron boost to the tumor bed. Most of the patients were followed routinely in the department for 2 to 5 years. The frequency of zoster was determined retrospectively by reviewing the patients' records. A zoster after radiotherapy occurred in 41/1,155 patients (3.7%), mostly within the first 2 years after completion of radiotherapy. All infections remained localized and there was no evidence for systemic infections. Type of treatment (mastectomy vs breast-preservation) had no impact on the frequency of herpes zoster (36/961 patients after mastectomy and 5/194 patients after breast-preservation). There was also no correlation with other prognostic factors such as age, menopausal status, stage of disease or the use of adjuvant chemotherapy, nor was the occurrence of zoster linked to the degree of acute skin reaction in the radiation field. Moreover, patients with zoster had the same prognosis as compared to patients without zoster with regard to local control and survival. The observed frequency of zoster (about 4% of patients after postoperative radiotherapy) in this retrospective study suggests that the risk of developing zoster in this patient group may be 3- to 5-fold higher as compared to the incidence in the general population. However, the occurrence of zoster was not linked to prognosis and treatment response.

Bronchial stump aspergillosis

Two cases of bronchial stump aspergillosis were diagnosed 5 and 6 years after pneumonectomy for lung cancer. In each case, the fungal mass was endoscopically removed using standard forceps. A recurrence of the fungal mass persisted until all visible protruding nylon threads in the airway lumen were destroyed with a Nd:YAG laser. Removal of the visible suture is necessary for eliminating the infection. No additional local or systemic antifungal therapy is needed.

Primary systemic therapy in operable breast cancer.

Laboratory studies suggest that primary systemic therapy (PST) could improve control of micrometastatic disease and impact on overall survival (OS). This article examines the rationale for and preclinical and clinical data of PST in operable breast cancer and the potential role of intermediate biomarkers as predictive and/or prognostic factors for response and survival. We conducted an extensive literative review (including MEDLINE) on preclinical studies, single-arm feasibility studies, large randomized single- and multi-institutional trials, and laboratory correlate studies of PST in breast cancer. Small trials in locally advanced disease showed high initial rates of response and local control. Six randomized clinical trials (RCTs) of PST for palpable, operable breast cancer have been reported since 1991 (from 204 to 1,523 patients each). These data clearly show a small but significant (less than 10%) absolute increase in the use of breast-conservation treatment (BCT) with similar rates of local control. Although one study showed better disease-free survival (DFS) and another showed better OS, most studies did not show any survival advantage of primary versus adjuvant systemic therapy. Thus far, pathologic complete response seems to be the best predictor of survival, but clinical response assessment correlates poorly with pathologic response. Pilot studies demonstrated feasibility of procuring tissue at diagnosis and after treatment for assays of potential intermediate biomarkers. Initial data suggest a potential correlation between markers of proliferation and apoptosis and in vivo chemotherapy sensitivity. Thus far, RCTs of PST versus standard adjuvant therapy have not shown any clear benefit for DFS or OS in early breast cancer. Ongoing trials should determine if specific subsets of patients at risk would benefit from additional systemic therapy and the potential role of intermediate biomarkers in identifying such women. Although PST results in a small increase in the rate of BCT with similar rates of local control, current PST strategies should not replace standard adjuvant approaches. Rather, they represent an acceptable alternative to women with palpable, operable tumors and an excellent arena for clinical trials.

Minimal residual disease in breast cancer.

The incidence of breast cancer is increasing dramatically in the developed countries. Although attention is being paid to diagnose breast cancer early through screening programs, still a significant number of patients classified to have a localised disease at diagnosis, later experience a systemic recurrence. Therefore, more sensitive and reliable methods to detect the early spread of the disease, permitting the early use of additional systemic therapy, seem justified. New treatment strategies, such as immunotherapy employing monoclonal antibodies against breast cancer cells, is promising. Since such a treatment is most efficient on patients with limited disease, sensitive methods to monitor the therapeutic effect are needed. Immunocytochemistry using tumour associated monoclonal antibodies and reverse transcription polymerase chain reaction assays (RT-PCR), that screen for carcinoma-specific expression of mRNA in bone marrow and blood, have been developed. Many standardisation problems with the detection methods currently in use are unsolved. Despite this, we discuss here recent data showing that the presence of occult tumour cells in the bone marrow is a prognostic factor in patients with breast cancer.

Differentiation of primary and secondary cutaneous B-cell lymphoma by Southern blot analysis.

Malignant B-cell lymphomas represent a heterogenous group of lymphoreticular disorders that involve the skin in about 20% of reported cases. Skin involvement may be primary or secondary (ie, the result of hematogenous spread). Primary cutaneous B-cell lymphomas (PCBCLs) are thought to take a comparatively favorable course, respond readily to nonaggressive treatment, and lack evidence of extracutaneous spread. Nine primary B-cell lymphomas (7 centrocytic or centroblastic follicular, 1 immunoblastic, 1 centroblastic), three secondary (follicular) cutaneous B-cell lymphomas (SCBCLs) and two pseudolymphomas were studied. Staging revealed that bone marrow was involved only in SCBCLs. Centrocytes were detected in blood smear preparations of all SCBCLs. All lymphomas were treated with local irradiation. Patients with primary centroblastic and immunoblastic cutaneous lymphomas and those with secondary lymphomas received additional chemotherapy. Pseudolymphomas were treated by simple excision. Patients were monitored on average for 55 months. During this period, no patients with PCBCLs exhibited cutaneous relapses or hematogenous spread. In contrast, all patients with SCBCLs experienced cutaneous relapses. Peripheral blood, bone marrow, and skin samples from all patients were subjected to Southern blot analysis using a JH probe. Clonal rearrangement was found in all skin samples investigated except specimens from pseudolymphomas. Peripheral blood and bone marrow samples were positive in SCBCLs (the rearrangement pattern was different from that of the skin samples for two of the three patients), whereas it was negative in all PCBCLs and pseudolymphomas. In conclusion, Southern blot analysis of peripheral blood may be useful in differential diagnosis of PCBCLs and SCBCLs and a prognostic marker. Furthermore, these data confirm the comparatively favorable clinical course of PCBCLs and suggest that in these cases, local irradiation can be considered adequate treatment, whereas SCBCLs require additional systemic therapy.

Systemic antimicrobial treatment and guided tissue regeneration Clinical and microbiological effects in furction defects

The purpose of this investigation was to study the microbiota associated with furcation-involved teeth before and after treatment by the guided tissue regeneration procedure (GTR) with non-resorbable ePTFE membranes, and to evaluate the benefit of additional systemic antimicrobial therapy (ornidazole). Each of 10 patients contributed 1 pair of bilateral mandibular molars with comparable furcation defects. 5 defects were treated with a membrane and the active drug, 5 were treated without a membrane but with the active drug, 5 were treated with a membrane and a placebo, and 5 were treated with neither a membrane nor the active drug. Considerable differences were found in the healing response of furcation defects treated with or without the antimicrobial agent. More horizontal attachment gain and increase in bone density was obtained in patients receiving the active drug than in patients receiving the placebo. With 1 exception, all sites with increasing horizontal probing depth were found in patients of the placebo group. Treatment with membrane plus ornidazole resulted in 0.7 mm mean recession and -1.2 mm mean decrease in horizontal probing depth. Sites treated with membranes generally tended to be positive for 15 target micro-organisms more often than sites treated without a membrane. This was particularly evident for Fusobacterium, Prevotella intermedia and Actinomyces odontolyticus. Whereas GTR-treated sites were often already positive upon removal of the membrane, re-emergence of target organisms seemed to be more delayed in the conventionally-treated sites.

Bronchial Stump Aspergillosis Four Years After Lobectomy

Bronchial stump aspergillosis (BSA) is an unusual entity. We report a case presenting hemoptysis four years after right upper lobe resection because of lung cancer. Simple removal of the silk suture is most likely the treatment of choice. No additional local or systemic antifungal therapy is needed.

Prognosis and treatment decisions in patients with breast cancer without axillary node involvement.

Every month, treatment decisions must be made for more than 6000 patients with breast cancer without axillary node involvement in the United States. Approximately 70% of these patients will survive more than 10 years after surgery and/or radiation treatment without additional systemic adjuvant therapy. If we had good methods to identify patients who are destined to have a recurrence of their disease, only those patients should receive adjuvant therapy. The authors reviewed the literature supporting the use of currently available prognostic factors for patients with node-negative breast cancer, and formulated a framework on which prognostic factor information can be based to help make these treatment decisions. The steps involved in making treatment decisions are: use prognostic factors to determine the recurrence probability; calculate the expected treatment benefit; and weigh the expected benefits against the potential risks. Prognostic factors can be used to help make treatment decisions for patients with breast cancer without axillary node involvement. However, the final treatment decision must take into account all aspects of the patient and her disease, and the physician must help the patient evaluate her prognostic factors, arrive at an understanding of her particular risk of recurrence, and weigh the potential benefits and risks of adjuvant therapy.

The role of resection in the treatment of pulmonary metastases from Ewing’s sarcoma

We have investigated the role of resection in the treatment of patients with isolated pulmonary metastases from Ewing's sarcoma. In a retrospective review, 19 patients with the diagnosis of Ewing's sarcoma treated at the National Cancer Institute from 1965 to 1985 who underwent chest exploration for resection of pulmonary nodules were evaluated. Ten patients (53%) were made disease free by resection of pulmonary metastases, six patients (32%) were found to have unresectable disease, and three patients (16%) were found to have benign pulmonary disease. The actuarial 5 year survival rate of the 10 patients successfully made disease free by resection was 15%, and the median survival of this group was 28 months. In contrast, the median survival of the six patients not made disease free was 12 months, and no patient with residual disease was alive 22 months after thoracotomy (p2 = 0.0047). There were no postoperative deaths and only three minor postoperative complications for 25 operative procedures. Various prognostic variables were analyzed to determine their influence on postmetastasectomy survival. There was no difference in postmetastasectomy survival between patients who underwent resection of synchronous versus metachronous pulmonary metastases (p2 = 0.90). Patients who underwent resection of fewer than four malignant nodules had a significantly longer postmetastasectomy disease-free survival (p2 = 0.0019) and overall survival (p2 = 0.06) than those undergoing resection of four or more nodules. Patients who underwent resection of metastases that developed during chemotherapy had a significantly shorter postmetastasectomy survival that those who underwent resection of metastases that developed after chemotherapy (p2 = 0.0295). Our data show that selected patients with Ewing's sarcoma metastatic to the lungs may benefit from an aggressive surgical approach. Also, a significant proportion of these patients will have benign pulmonary disease and can thus avoid additional intensive systemic therapy.

Systemic high-dose ara-C for the treatment of meningeal leukemia in adult acute lymphoblastic leukemia and non-Hodgkin's lymphoma.

Considering the good penetration of systemic high-dose ara-C (HDara-C) into the CNS, we used this approach for treating overt meningeal leukemia, either isolated or with concurrent extraneurologic disease, in 15 adults with high-risk acute lymphoblastic leukemia (ALL), one adult with lymphoid blast crisis of chronic granulocytic leukemia (LBC-CGL), and four adults with poor-prognosis non-Hodgkin's lymphoma (NHL). Treatment consisted of ara-C, 3 g/m2 every 12 hours by three-hour infusion for eight doses followed by a second course of four doses on day 21. Remitters received consolidation with monthly courses of HDara-C for four doses. Additional systemic multi-drug reinduction therapy and direct CNS treatment with intrathecal methotrexate (IT MTX) and cranial irradiation (CRT) was administered to the three remitters last treated. Thirteen of 20 patients (65%) achieved complete remission (CR): seven of seven patients with isolated meningeal leukemia and six of 13 patients with concurrent CNS and bone marrow disease. Of the remaining seven patients, five had a complete CSF clearing with persistent marrow disease. In all cases there was prompt resolution of neurologic signs and symptoms. The median duration of CR was 5 months (range 2 to 8 months). The most significant toxicity seen was myelosuppression, which was predictable and manageable. Nonhematologic toxicity was generally acceptable and included moderate nausea and vomiting, diarrhea, drug fever, transient liver dysfunction, and dermatitis. No cases of CNS toxicity occurred. There were no treatment-related deaths. Disease-free survival was limited by marrow relapse, either isolated or with concurrent CNS disease. No instances of isolated meningeal relapse occurred. These results obtained in a poor-risk subset of patients indicate that HDara-C is an effective treatment for the induction of remission in ALL and NHL with meningeal leukemia. Therefore, HDara-C should be considered for inclusion in multiagent consolidation programs for patients at high risk for CNS disease.

Serum gentamicin concentrations during intratracheal administration.

In artificially ventilated patients, intratracheal aminoglycoside administration is used as a form of prophylaxis of broncho-pulmonary infections. In artificially ventilated patients with multiple organ failure, serum gentamicin concentrations were measured dependent on renal function after endotracheal administration. A standard commercial ampule of 40 mg gentamicin in a 1 ml solution was injected in undiluted form, intratracheally through the tubus , every 6 h. In the patients without renal failure, values over 1 microgram/ml were only found in certain individual cases and reached a maximum of 1.5 micrograms/ml. In patients with renal failure even after prolonged application, the average serum concentrations were between 2 and 3.5 micrograms/ml. In a very few cases, however, levels of up to 10.5 micrograms/ml were measured. The daily serum pattern revealed a distinct dependence on the administration; 1 h after administration there was an increase in the serum concentrations which decreased to the initial levels after 6 h. When patients with renal impairment are given an aminoglycoside intratracheally, serum levels of up to 10.5 micrograms/ml may be reached and thus additional systemic aminoglycoside therapy should be avoided.

Carcinoma of the endometrium.

Controversy continues as to how and when radiation therapy can best be combined with surgery in order to improve treatment results in patients, with endometrial cancer. Various prognostic factors--tumor grade, depth of myometrial invasion, size of the uterine cavity, and the presence of nodal or parametrial spread--must all be considered when planning therapy. Well-differentiated Stage IA endometrial cancers hav an excellent prognosis when treated by surgery alone. Evidence suggests, however, that all other Stage I tumors benefit from combined radiation and surgical treatment. Patients with advanced stages of disease are candidates for combined surgery and radiation or radiation alone, owing to the high frequency of pelvic node involvement. Areas of active investigation include the addition of systemic therapy in patients with Stage III disease and the evaluation of extended field radiation in patients with histologically confirmed high pelvic or paraaortic nodal involvement.