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PubMed2004

[Neoadjuvant chemotherapy for symptomatic non operable grade II fibrillary astrocytoma in adults].

We collected 6 case-reports of symptomatric non removable low grade fibrillary astrocytoma of adults treated with a procarbazine-CCNU-vincristine chemotherapy regimen. All patients had drug-resistant epilepsy but brain imaging was stable. Total gross resection was rejected because of Volume or tumor location. After 4 to 7 cycles of chemotherapy, 2 patients had partial response and one minor response on brain MRI. All of them were seizure-free. Progression free survival was not reached at 5 Years. Up-front chemotherapy for low-grade astrocytomas may be useful and has to be prospectively evaluated.

Adult↗
PubMed1953

Wiltshire bacon.

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Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

Oligodendroglioma and anaplastic oligodendroglioma: clinical features, treatment, and prognosis.

BACKGROUND: Recent advances that have been made in diagnostic imaging, surgical technique, chemotherapy, molecular biology, and prediction of therapeutic response could have potential impact on the optimal diagnosis and treatment of patients with brain tumors, especially those with oligodendrogliomas. In this article, the topic of oligodendroglioma and anaplastic oligodendroglioma is reviewed, highlighting the new clinical developments. METHODS: Information for this review was obtained by performing a Medline search for recent references using the term "oligodendroglioma." The bibliographies of papers obtained also were checked for articles that could provide additional understanding of this disease and its current treatment. RESULTS: The incidence of oligodendroglioma is increasing, most likely due to its improved recognition. Seizures and/or headaches are still common presenting features, and surgery continues to be the primary treatment. Positron emission tomography (PET) and molecular analysis of the surgical specimen are emerging as important diagnostic tools. Patients having either oligodendroglioma or anaplastic oligodendroglioma are likely to respond to chemotherapy. This has had an impact upon the timing of radiation therapy. Survival times are increasing, and patients can now be divided into prognostic subgroups based on the molecular features of their tumors. While procarbazine-CCNU-vincristine (PCV) chemotherapy has been the standard, other agents, notably temozolomide, are currently being tested. CONCLUSIONS: The algorithm for diagnosing and treating patients with oligodendrogliomas has changed. Neurosurgeons need to be aware of the new developments so they can offer sound advice to their patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

The role of PCV chemotherapy in the treatment of central neurocytoma: illustration of a case and review of the literature.

BACKGROUND: Most central neurocytomas follow a benign clinical course. However, more aggressive variants have been described requiring additional surgical resection, radiation, or chemotherapy. Chemotherapy has rarely been used as an adjuvant therapy for central neurocytomas. METHODS: We report a case of a 20-year-old girl who underwent four subtotal resections, over the course of 3 years, for a large central neurocytoma that continued to progress. She was not a candidate for stereotactic radiosurgery, given the large tumor size. To avoid radiation injury in a young patient, she was treated with six cycles of chemotherapy including procarbazine, CCNU, and vincristine. Procarbazine was stopped after 2 cycles because of the development of a rash. Serial magnetic resonance imaging was used to follow treatment response. RESULTS: Her tumor started to decrease in size after 2 cycles of chemotherapy and continued to shrink until it stabilized after 5 cycles of chemotherapy. A small area of residual tumor with minimal enhancement persisted along the left lateral ventricle and remained stable for at least 16 months after the completion of chemotherapy. CONCLUSIONS: To our knowledge, this is only the fourth report describing the use of chemotherapy for progression of central neurocytomas as a treatment alternative to radiation therapy. The use of procarbazine, CCNU, and vincristine has not been previously described for the treatment of a central neurocytoma and presents an additional treatment option.

Adolescent↗
PubMed2001

Chemotherapy for the treatment of oligodendroglial tumors.

Oligodendroglial tumors include the highly chemosensitive oligodendroglioma and mixed oligoastrocytoma. Patients with these tumors have a longer median survival and time to disease progression than patients with other brain tumor types, but the range is wide and the disease is inevitably fatal. Because of their chemosensitivity and the potential for radiation toxicity, low-grade oligodendroglioma are increasingly being treated with adjuvant or neoadjuvant chemotherapy before radiation therapy. Approximately two thirds of patients with the more aggressive form (anaplastic oligodendroglioma) have shown substantial response to first-line procarbazine/lomustine/vincristine (PCV) therapy. However, experience with chemotherapy for relapse of disease following PCV therapy is limited. Several small trials have shown the safety and activity of temozolomide (Temodar in the United States, Temodal globally; Schering Corporation, Kenilworth, NJ) in oligodendroglioma, regardless of prior PCV therapy. An open-label, phase II trial of temozolomide in 47 patients with relapsed oligodendroglioma showed an objective response rate of 43%, of which seven (15%) were complete responses. Median progression-free survival was 6 months and 34% of patients were disease-free at 12 months. Median survival was 26 months for complete responders and 11 months for partial responders. Temozolomide was well tolerated. The only grade (3/4) toxicity with temozolomide treatment was thrombocytopenia, which occurred in < or = 5% of the 382 treatment cycles administered. The encouraging results of ongoing trials with temozolomide suggest the potential for its use as a first-line therapy in this patient population.

Antineoplastic Agents, Alkylating↗
PubMed1981

Metastatic tumor to the retina and vitreous cavity from primary melanoma of the skin: treatment with systemic and subconjunctival chemotherapy.

The cases of two young women with metastatic tumors to the retinas and vitreous cavities from primary melanoma of the skin are discussed. Each presented with 20/20 central visual acuity in both eyes and complaints of floaters related to singularly unusual golden brown cellular aggregates infiltrating the vitreous cavities. Some cells appeared to be emanating from the region of the optic nerves whereas others appeared to originate from the superficial retina, presumably from the retinal vessels. The cellular aggregates were comprised of malignant melanoma cells as determined by histocytology of a vitrectomy specimen in one case and an aqueous aspirate in the other. The clinical appearance of cellular aggregates in the form of regular spherules should alert the clinician to the possibility of malignant rather than inflammatory cellular infiltration. The combined administration of repeated systemic and subconjunctival DTIC in case 1 and BCNU in case 2 was unsuccessful in promoting tumor regression. Histology of one eye, removed because of uncontrolled neovascular glaucoma, revealed numerous melanoma cells in the superficial retina and adjacent vitreous.

Adult↗
PubMed1987

The efficiency of different combined treatment programs (combination chemotherapy-radiotherapy) used for stage I-II Hodgkin's disease.

This study presents the analysis of results obtained in 237 Hodgkin's disease patients, stages I and II, treated with combined modality therapy. The overall and disease-free survival rates at 5 years were 96.6 and 85.2%, respectively. The study has demonstrated the superiority of the following treatment program: one cycle of combination chemotherapy + radiation therapy + 5 cycles of combination chemotherapy. It has been found possible to reduce the number of radiation fields in combined modality therapy: for patients with stage IA-IIA lymphocyte predominant or nodular sclerosing Hodgkin's disease it was sufficient only to treat clinically involved sites. Short- and long-term consequences of combined modality therapy have been analysed.

Adult↗
PubMed1995

Oral therapy for small cell lung cancer.

After a remarkable improvement of the very poor prognosis of small cell lung cancer with very simple therapy such as iv and oral cyclophosphamide the role of oral therapy has become minimal. However, since more than a decade results of combination chemotherapy are at a plateau and it is necessary to reconsider the role of simple therapy in patients without the prospect of cure. Oral therapy might be worthwhile because it is probably less effecting the quality of life of the patient and makes it unnecessary to visit the hospital frequently. All drugs available for oral use with known activity against small cell lung cancer are reviewed. The best example of the success of oral therapy is etoposide, other candidates that need to be tested in a modern way are oral cyclophosphamide and hexamethylmelamine. New concepts of prolonged chemotherapy and dose-intensity are easier evaluated by using oral drugs. The discovery of the activity of prolonged oral etoposide is an excellent example how to test a new concept in a very simple way.

Administration, Oral↗
PubMed1997

Efficacy of platinum-based regimens in non-small cell lung cancer. A negative report from the Cuneo Lung Cancer Study Group.

Combination chemotherapy with cytotoxic agents is the regular treatment for patients with advanced non-small cell lung cancer (NSCLC), good performance status, and no major clinical contraindications. Since the early 1980s, platinum-based chemotherapy is the cornerstone of this treatment, while combinations containing long-acting alkylating agents have been nearly abandoned, and represent a sort of historical treatment. Nevertheless, the real survival benefits of cisplatin are uncertain and still debated. To attempt an answer, the Cuneo Lung Cancer Study Group (CuLCaSG) carried out a clinical trial comparing a platinum (MVP) versus a non-platinum-based combination chemotherapy (MACC). The study comprised 156 patients with advanced NSCLC randomly assigned to the two treatment arms. MACC and MVP chemotherapies were given as originally described and continued until progression of disease, unacceptable toxicity, or refusal by the patient. For a medium of four cycles of MVP and three cycles of MACC, the median dose intensity (DI) reached was, respectively, 95% and 100% of the intended (P = 0.0132). In all, 27 objective responses (1 complete and 16 partial responses in patients allocated to MVP versus 10 partial responses of the MACC group) were observed. Median progression-free and global survivals were, respectively, 21 and 34 weeks for MVP and 20 and 31 weeks for MACC (non-significant differences). The treatment plan was found non-significant also multivariate analysis of survival. Toxicity was rather similar in the two arms, except for more severe neurological toxicity, anemia, thrombocytopenia, nausea, and vomiting in patients on MVP. Alopecia was more common after MACC. Subjective tolerance to treatment, and perception of physical and psychological well-being were rated similarly by patients of both groups. In conclusion, MVP was moderately more active than MACC, and showed a foreseeable and reversible toxicity, of a low-medium grade. However, this CuLCaSG study failed to substantiate any survival benefit from the use of platinum in combination with other cytotoxic agents.

Aged↗
PubMed1999

Standard combination versus alternating chemotherapy in small cell lung cancer: a randomised clinical trial including 394 patients. 'Petites Cellules' Group.

PURPOSE: to compare standard and alternating administration of chemotherapy combinations in small cell lung cancer (SCLC) patients. MATERIAL AND METHODS: in a multicenter clinical trial, 394 previously untreated SCLC patients were randomised to receive, every 4 weeks, eight courses of either a standard regimen with CCNU, cyclophosphamide, adriamycin (CCA) and VP16 or an alternating regimen (CCA regimen alternating with cisplatin-vindesine-VP16). RESULTS: overall response rate was higher in the standard group (78%) than in the alternating group (64%) (P = 0.0001). Complete response rate was also higher in the standard group (32%) than in the alternating group (18%) (P = 0.004). The median survival in the overall SCLC population was 306 days in the standard group and 272 days in the alternating group (P = 0.08). In limited SCLC patients, median survival was higher in the standard group (421 days) than in the alternating group (328 days) (P = 0.01). Grade III/IV haematological toxicity was lower in patients in the alternating group (25 versus 47%) (P < 0.001). CONCLUSION: the standard regimen was better than the alternating regimen for patients with limited forms of SCLC. The alternating regimen, associated with better haematological safety and ensuring a fairly similar survival, may be considered in patients with extensive SCLC. Pleiomorphic resistance mechanisms to chemotherapy make it difficult to define a non-cross-resistant chemotherapy regimen.

Adult↗
PubMed1983

Photocarcinogenesis, skin cancer, and aging.

Nonmelanoma skin cancers, like most malignancies, increase in incidence with increasing age. However, in general they are not due to the aging process but are primarily due to solar radiation. Clinically, squamous cell carcinomas and basal cell epitheliomas are the most common cancers that occur in the Caucasian population in the United States. The role of radiation from the sun was suggested by a number of astute clinical observations reported around 1900 and subsequently has been established by epidemiologic and experimental studies. Action spectrum evaluations indicate that the ultraviolet B (UVB) rays are the most carcinogenic. However, recent studies indicate that the UVA rays can augment the cancer-producing effects of UVB rays. Other physical stimuli, including heat and wind, can also accelerate UVB carcinogenesis. Chemicals such as the polycyclic hydrocarbons, the nitrosoureas, and nitrogen mustard have an additive carcinogenic effect with UVB radiation. Also, some chemicals such as croton oil, the phorbol ester--TPA, and all-trans-retinoic (RA) acid can promote UVB-initiated carcinogenesis. RA can also inhibit UVB-induced cancer formation. The role of the immune status has received a great deal of attention. Both in experimental and clinical situations, nonspecific immune suppression results in increased cancer formation. Also, recent studies indicate that a specific T cell suppressor population can be induced in experimental animals with UVB which will inhibit rejection of tumors produced by UVB radiation. Finally, damage to DNA by UVB radiation is well established. Studies with the genetic disease xeroderma pigmentosum support the concept that such damage, if not repaired, will lead to cancer formation. It also has been suggested that unrepaired damage to deoxyribonucleic (DNA) and other macromolecules is at least in part responsible for the aging process in general.

Aging↗
PubMed1986

Karyometric, cytophotometric and histoenzymatic studies on neuroglia of rats treated with 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU/lomoustine).

CCNU is a cytostatic drug, a nitrosourea derivative, used--among others--in therapy of tumors of the central nervous system. Even if the drug is regarded safe for central and peripheral nervous systems, a possibility of harmful effects of CCNU on the central nervous system should be examined caused by the affinity of all nitrosourea derivatives to lipids. This has prompted us to study the drug effect on neuroglia cells in corpus callosum and gyrus cinguli. The drug was administered to rats by the intragastric route in four doses--one dose a week. Three doses of 2.5 mg each were followed by one dose of 5 mg. Some brains were isolated for the studies, and paraffin sections were prepared for karyometric as well as cytophotometric studies and for section staining according to Nissl and Klüver-Barrer techniques 8 days after the last dosage. Brains of other experimental rats served for preparing cryostat sections for demonstration of phosphatase and esterase activities. The studies, conducted after CCNU administration, documented a significant decrease in size of oligodendroglia nuclei and an increase in size of astroglia nuclei. DNA content of neuroglia nuclei was markedly decreased. Histoenzymatic changes in experimental animals were not very pronounced and included a slight increase in TPPase and nonspecific esterase activities as well as a decrease in ATPase activity. Despite the changes in neuroglia cells no damage to corpus callosum myelin sheaths was observed.

Adenosine Triphosphatases↗
PubMed1978

The effect of combination chemotherapy on the reticuloendothelial system in man.

The effect of adjuvant combination chemotherapy (vincristine, CCNU/MeCCNU, 5-fluorouracil) on the phagocytic and catabolic properties of the reticuloendothelial system (RES) was studied in 4 patients before and during the anticancer treatment. The results indicate a transient impairment of both these functions, more prolonged with regard to phagocytosis. No significant changes were noted in the mobile macrophage system. This suggests that chemotherapy induces a depression especially of the stationary macrophage populations in the liver, spleen and bone-marrow.

Aged↗
PubMed1986

Clinical studies of autologous bone marrow transplantation in Hodgkin's disease.

Approximately half of conventional-chemotherapy-resistant, far-advanced Hodgkin's disease patients can be placed into remission with existing intensive therapy regimens and ABMT; these results are similar to those noted in less-heavily pretreated non-Hodgkin's lymphoma patients. While a few of these end-stage patients have prolonged remissions, failure frequently occurs in a pattern that suggests the inadequacy of the intensive regimens rather than reinoculation of malignant cells in the marrow autograft. The use of additional local radiotherapy may be helpful in selected patients, and more effective regimens may be developed in the future. However, treatment of less advanced disease is primarily indicated. Due to previous treatment features, patients with advanced Hodgkin's disease may have more morbidity and mortality than a similar group of non-Hodgkin's lymphoma patients. This problem can be minimized by better patient selection, earlier marrow storage and the avoidance of TBI-containing regimens in patients at high risk of interstitial pneumonitis. Routine marrow purging is unlikely to be required for Hodgkin's disease patients given ABMT. The use of intensive therapy and ABMT for the treatment of Hodgkin's disease is currently indicated most clearly for treatment of a patient in initial partial remission, early relapse from an initial chemotherapy-induced remission, or consolidation of a second remission reinduced by conventional therapy.

Alkylating Agents↗
PubMed2001

Radiotherapy of esthesioneuroblastoma.

PURPOSE: Only 3% of all malignant intranasal tumors are esthesioneuroblastomas (ENB). As the tumor is very rare, the number of ENB treated in individual departments is small. In order to evaluate the efficacy of radiotherapy (RT), patients' data of 2 centres were analysed with reference to new reports in literature. METHODS AND MATERIALS: From 1981 to 1998, 17 patients with ENB, 8 men and 9 women aged between 6 and 81 years, were treated in the departments of radiotherapy of the universities of Cologne and Muenster. The tumors were Kadish Stage B in 4/17 patients and Stage C in 13/17 patients. Treatment included incomplete surgery and irradiation in 2/17 patients, adjuvant RT postoperatively in 6/17 patients, definitive RT in 7/17 patients and RT after incomplete surgery of recurrent tumors in 2/17 patients. Postoperatively, the median target dose of EBRT was 56 (range 50-60) Gy; for definitive RT it was 58 (range 40-70) Gy. RESULTS: After a median follow-up period of 86 (range 2-208) months 10/17 patients showed no evidence of disease (NED). There were 6 patients treated with radical complete surgery plus postoperative irradiation and 5 of them were NED. There were 7 patients treated with only irradiation and 3 of those patients were NED. Of 2 patients with incomplete surgery and irradiation there was one patient NED. Of 2 patients with incomplete resection of recurrent tumor who received irradiation, there was one patient NED. 2 of the patients with NED died after 22 and 94 months respectively. 4/17 patients died as a result of local recurrence and 2/17 patients as a result of distant metastases (liver, brain). One patient with a recurrent tumor is alive. Median survival of all 17 patients was 94 months. Progressive disease after definitive RT occurred after a median of 11 months. CONCLUSION: Esthesioneuroblastomas are radiocurable tumors. In correlation to literature a primarily complete tumor resection followed by adjuvant RT (50-60 Gy) offers the best disease free survival.

Adult↗