Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

16 patients with an advanced stage SCLC were treated with the use of aggressive chemotherapy with bone marrow transplantation. With the gaining of experience the doses have been increased from standard-dose induction and 7 g/m2 of CTX in intensification to more aggressive induction (160 mg/kg of bw of CTX and 1.6 g/m2 VP-16 in two courses in 28 days interval) and intensification (CTX 7 g/m2 and VP-16 from 1.5 to 2.0 g/m2. Most recently, we used the following intensification which, in addition to the high dose CTX (6 g/m2), consisted of VP-16 0.9 g/m2 and BCNU 0.5 g/m2. The procedure proved to be safe. Hematological recovery emerged in all patients at a very similar time after autografting, irrespective to the late intensification regime. All cases, except one, received, after the hematological recovery, prophylactic cranial and at the primary tumor site irradiation as well as 2 to 4 courses of standard dose maintenance chemotherapy. The response rate was higher in the group receiving more aggressive induction and intensification. Long-term survival was seen only in patient which received more aggressive induction and intensification. Median survival of all cases was 13 months including 3 cases which are disease-free 24, 21 and 14 months after the beginning of the treatment.
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PMID:Aggressive chemotherapy with autologous bone marrow transplantation in small cell lung carcinoma. 166 52

Between 1968 and 1980, 107 consecutive patients with Ewing's sarcoma of bone were entered on three sequential combined modality treatment protocols (S2, S3, S4) at the National Cancer Institute (NCI). Protocol treatment involved 4 cycles of two drug [cyclophosphamide (CTX) and vincristine (VCR)] or three drug [CTX and VCR with either actinomycin-D (ACT-D) or doxorubicin (ADR)] regimens and local irradiation (50 Gy) to the involved bone. Eighty patients presented with localized disease and 27 patients had metastatic disease at presentation, including 11 patients with multiple metastatic sites. With a median potential follow-up of greater than 15 yrs (range 8-20 yrs), 28 pts (27%) remain alive. Disease-free (DFS) and overall survival (OS) decreased most rapidly during the initial 5 yrs of follow-up with 5-yr DFS of 29% and 5-yr OS of 39%. Only two patients with metastases at presentation are long term (greater than 5 yr) survivors. For localized disease patients, the 2, 5, 10, and 15 yr DFS and OS are 52%, 37%, 35%, and 33% DFS and 68%, 51%, 39%, and 34% OS, respectively. Eleven patients relapsed locally as the first site of failure. Using the Cox proportional hazards model, four significant variables for both DFS and OS were recognized, including metastatic disease at presentation, age greater than 25 yrs, high LDH in localized disease patients, and central primary tumor in localized disease patients in decreasing order of significance. We conclude that a majority of these patients with Ewing's sarcoma of bone relapsed within 5 yrs of presentation although late relapse (5-15 yrs) did occur. Local failure occurred in 20% of patients using these combined modality treatments but had no impact on overall survival.
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PMID:Long-term follow-up of Ewing's sarcoma of bone treated with combined modality therapy. 199 54

The object of the present investigations was delineation of the exclusive effects of cyclophosphamide (Cytoxan) on host humoral response to tumor, as evaluated by the level of circulating antigen/antibody complexes (AACs), which may reflect the chemo-responsiveness of hosts and provide a rationale for new therapeutic strategies. Our data, recorded in Copenhagen X Fischer rats bearing Dunning's R-3327 Mat Ly-Lu adenocarcinoma of the prostate, show no modulatory effect of cyclophosphamide at 10 mg/kg, a nonspecific immunosuppressive effect at 30 mg/kg, and a definite immunostimulatory effect on host humoral immunity at 100 mg/kg. Sequential determination of AAC levels at different stages of tumor growth, i.e. from the primary to the metastatic stage, performed with the original purpose of demonstrating that any disturbance in the immunoregulatory mechanism of the host was due to cyclophosphamide rather than to changes in tumor load, revealed that levels of AACs parallel disease progression in the initial stages of primary tumor growth but rapidly decrease to near-normal levels in the presence of heavy tumor burden.
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PMID:Immunomodulatory effect of cyclophosphamide on host humoral immunity in Dunning's R-3327 adenocarcinoma of the prostate. 202 60

From 1979 to 1986, 182 patients with biopsy proven diagnosis of Ewing's sarcoma of bone were observed. One hundred of the 182 patients (72 males, 28 females, median age 15.8 years) with localized disease and no previous treatment were treated with chemotherapy (VCR, ADM, CTX, D-ACT) for 15-18 months. Local treatment was radiotherapy (42 patients), surgery (31 patients), or a combination of both (27 pts). Radiation doses ranged from 45 to 64 Gy given with conventional fractionation. Median follow-up was 51.2 months (24-106). Overall and disease-free survival were, respectively, 58.7 and 42.6%. Resected patients tended to have a better local control (Surgery 93.6%, Surgery + Radiation therapy 92.6%, Radiation therapy 69.1%). Disease-free survival was significantly related to the volume of the primary tumor (bulky: 33.2%, not-bulky: 57.7%), to site (extremities 54.6%, central sites 16.6%, other sites 40.9%), and to local treatment (Radiation therapy 30.3%, Surgery + Radiation therapy 47.9%, Surgery 59.1%). These results are, however, biased because resected patients tended to have smaller tumors in favorable sites.
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PMID:Combined therapy of localized Ewing's sarcoma of bone: analysis of results in 100 patients. 225 7

We have evaluated the role of radiotherapy in providing local control of primary tumors and to palliate metastases from neuroblastoma (NB). Fifty-five children with histologically verified NB were evaluated and treated from 1967 to 1984. In univariate analysis, the actuarial survival of eight children with thoracic primaries (85%) was significantly better than the survival of 39 children with intra-abdominal primaries (35%, p = 0.0287). The survival of 28 children less than or equal to 18 months of age at diagnoses was 73%, whereas 27 children older than 18 months had a survival probability of 10% (p = 0.0001). The survival by Evans stage was: I 100% (2 patients), II 85% (7), III 60% (13), IV 4% (27) and IV-S 100% (6). According to the Pediatric Oncology Group (POG) staging system, the survival was: A 100% (3), B 66% (9), C 66% (9), D 23% (34). A multivariable analysis indicated that the Evans staging system was a more powerful indicator of prognosis than the POG system. The analysis also indicated that Evans stage and patient age were independent determinants of survival. The primary tumor site did not add significant prognostic information beyond these two factors. Children with Stage I disease were treated with surgery alone. Most children with Stages II and III disease were treated with surgery, irradiation, and Cyclophosphamide or Cyclophosphamide plus Vincristine. All seven patients with Stage II disease received post-operative irradiation to the primary tumor and were locally controlled with doses of 4.8 to 26.5 Gy. Eleven of the 13 patients with Stage III disease were irradiated post-operatively. Seven of these 11 patients were locally controlled with doses of 12 to 48.4 Gy. The four Stage III patients with in-field recurrences were older children with large radiotherapy fields and/or low doses administered. The Radiation Therapy Oncology Group pain score system was used to evaluate response of painful bony metastases to irradiation. A response was observed in 65% of the sites irradiated. A response was observed at 67% of the soft tissue metastases irradiated. Hepatomegaly causing respiratory embarrassment or inferior vena cava obstruction was treated with irradiation in seven patients. All patients responded with doses ranging from 5 to 24.4 Gy. Five of the 17 children who survived for more than 5 years following treatment had significant scoliosis or kyphosis secondary to vertebral body abnormalities in irradiated bones. All five children were irradiated at a young age with megavoltage equipment.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Radiation therapy in the management of neuroblastoma: the Duke University Medical Center experience 1967-1984. 242 88

From October 1979 to December 1982, 126 patients with locally advanced unresectable or inoperable Stage II (7 patients), Stage IIIA (81 patients), and Stage IIIB (38 patients) non-small cell carcinoma of the lung were treated in a prospective randomized trial using five cycles of CAP (Cytoxan, Adriamycin, and cisplatin), T-CAP (triazinate plus CAP), or V-CAP (VP-16 plus CAP) chemotherapy with thoracic radiation therapy (TRT). TRT consisted of 40 Gy in 10 fractions (split-course) with cycles 3 and 4 of chemotherapy. The treatment field included the primary tumor, ipsilateral hilum, mediastinum, and ipsilateral supraclavicular fossa. All patients were followed until death or for a minimum of 5 years for survivors. The evaluable subgroup consisted of 102 patients who completed TRT. Median and 5-year survivals for the entire group were 14.0 months and 10%, respectively; for the evaluable subgroup, they were 14.8 months and 12%, respectively. There was a trend toward better survival with V-CAP plus TRT than with CAP plus TRT (p = 0.08). Median and 5-year survivals were 16.2 months and 18%, respectively, with V-CAP plus TRT. Of eight prognostic variables analyzed for their association with survival, only Eastern Cooperative Oncology Group performance status (0,1 versus 2) (p = 0.02) and weight loss (less than or equal to 10% versus greater than 10%) (p = 0.05) were significant. Sex, age, T stage, N stage, overall stage, and histologic type were not significantly associated with survival. Failure analysis revealed 83 patients (81%) with identifiable first failures. The median time to first failure was 9.8 months, and the median survival after first failure was 4.7 months. Failure patterns included local failure alone (19%), local and distant (20%), and distant alone (43%). Nineteen percent of patients had no documented progression. Total failure patterns were local in 39% and distant in 63%. Twenty-three patients (23%) had failure in the brain; they accounted for 31% of all distant failures. In 20 of these patients (20% of all patients), this was the only site of failure. There were eight (8%) initial nodal failures in 96 untreated contralateral supraclavicular fossae. No initial failures were seen in any of 101 untreated contralateral hila. The data suggest the following: (a) Combined treatment with V-CAP and TRT yielded excellent results (median survival, 16.2 months; 5-year survival, 18%).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Results of combination chemotherapy and thoracic radiation therapy for unresectable non-small cell carcinoma of the lung. 255 4

Human ovarian carcinomas (HOC) were established s.c. and i.p. in nude mice and the biological characteristics were investigated for 4 xenografts. HOC8 and HOC18, derived respectively from a primary tumor of the ovary and a pleural effusion (from 2 different patients) were established s.c. in nude mice. HOC10 and HOC22, derived from the ascites of 2 patients, were directly established as ascites after i.p. injection in nude mice. The s.c. and i.p. growth behavior of the 4 HOC lines was investigated. HOC18, HOC8 and HOC22 cells produced progressively growing tumor after s.c. injection but HOC10 ascites would not grow s.c. The cell suspension derived from HOC18 only produced carcinomatosis upon i.p. injection, while HOC8 cells produced both ascites and carcinomatosis. The 2 ascites HOC10 and HOC22 produced ascites in nude mice, but only HOC22 formed i.p. carcinomatosis. Histopathological characteristics of the patients' primary tumors persisted in nude mice, regardless of the site of tumor implantation. DNA histograms of the xenografts closely matched the patients' tumors and remained stable at different passages. Cisplatin, adriamycin and cyclophosphamide given i.v. were tested against HOC8 and HOC18 growing s.c. and HOC22 and HOC10 growing i.p. HOC8 showed a significant response to DDP and almost no sensitivity to ADR and CTX. HOC18 showed only moderate growth delay with all 3 drugs. Mice bearing HOC10 and HOC22 ascites had a prolonged survival time after DDP and ADR treatment.
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PMID:Intraperitoneal and subcutaneous xenografts of human ovarian carcinoma in nude mice and their potential in experimental therapy. 277 13

We performed a randomized study from February 1979 to August 1981 in patients with small-cell lung cancer (SCLC) with the aim of defining the potential advantages of replacing vincristine (VCR) with vindesine (VDS), at that time a new semisynthetic vinca alcaloid, in the classical two-drug combination cyclophosphamide (CTX)-VCR. A total of 116 previously untreated patients were admitted to the study. Of 104 patients evaluable for response, 49 had limited disease and 55 extensive disease. Patients received 10 mg/kg CTX i.v. on days 1-4 and either 1 mg VCR i.v. or 2 mg/m2 VDS i.v. on days 1 and 4, and repeatedly every 4 weeks for 12 courses. In addition, the patients with limited disease received split-course radiotherapy (30 Gy/10 F, 3 or 5 weeks rest, 25 Gy/10 F, total treatment time 7 or 9 weeks) to the primary tumor, the mediastinum, and the supraclavicular areas between the second and third cycles of chemotherapy. The response rate to the first two chemotherapy cycles was 47% (4 complete response [CR] and 22 partial response [PR]) to CTX-VCR and 47% (4 CR and 19 PR) to CTX-VDS. Subsequent to radiotherapy the response rate increased to 93% for CTX-VCR and 100% to CTX-VDS, respectively, in the patients with limited disease. Local recurrence and/or progression occurred in 49% of limited disease responders and in 96% of extensive disease responders. In responders with limited disease, the first site of relapse was loco-regional in 25% for the VDS group as opposed to 15% in VCR group. In the patients with extensive disease, the corresponding figures were 62% for the VDS and 50% for the VCR group. Median duration of remission in all patients treated with CTX-VCR was 132 days compared to 203 days in the CTX-VDS group (not significant, NS). Median survival was 338 days for CTX-VCR vs. 342 for CTX-VDS in patients with limited disease, and 214 days for CTX-VCR vs. 312 days for CTX-VDS in extensive disease (NS). One-year survival figures were 47% for CTX-VDS and 35% for CTX-VCR patients. Two-year survivals were 4 and 9%, respectively. Neurotoxicity was the main toxic manifestation in both treatment groups. Severe peripheral neuropathy (grade 4, World Health Organization [WHO]) did not occur with either drug regimen. Treatment was discontinued because of grade 2-3 neuropathy in one patient after 6 cycles of CTX-VCR and in five patients after 1-6 cycles of CTX-VDS.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Vincristine-cyclophosphamide, the classical two-drug regimen for small-cell lung cancer, evaluated in a randomized study with vindesine. 282 8

Patients with limited stage small cell lung cancer were initially randomized to receive either three courses of Cyclophosphamide, Adriamycin, and Vincristine (CAV) followed by three courses of VP-16 and Cis-platin (VP-PT) or six courses of alternating CAV and VP-PT. Responding patients received prophylactic cranial radiation (PCI) after three courses of chemotherapy (CT) and loco-regional thoracic radiation (LRTR) after six courses. No maintenance chemotherapy was given. Patients receiving LRTR were randomized to receive either 25 Gy in ten fractions over 2 weeks (SD) or 37.5 Gy in 15 fractions over 3 weeks (HD). In both arms the pre-chemotherapy disease was treated with a 2 cm margin around the primary tumor volume. The mediastinum was included in the treatment volume and the supraclavicular nodes were also included if involved originally. The spinal cord was shielded after 32 Gy. Of the 333 patients enrolled by the time the trial closed in October 1984, 168 were eventually randomized to LRTR and are eligible for response assessment. The overall response rate after combined RT and CT was 94% (CR 67%, PR 27%). The CR rate for SD was 65% and for HD 69%. The combined treatment was well tolerated by most patients. Forty-nine percent of HD patients developed dysphagia compared to 26% of those SD (p less than 0.01). At the time of this analysis the median duration of follow-up since randomization to radiotherapy is 30 months. The median local progression-free survival on HD is 49 weeks. On SD it is 38 weeks (p = 0.05, one sided). The actuarial incidence of local progression by 2 years is 69% on HD and 80% on LD. There is as yet no significant difference in overall survival between the two arms. It appears that HD radiotherapy as administered in this study may have an impact on local control, but it is too early to determine if this will translate into a survival benefit.
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PMID:The effect of dose of thoracic irradiation on recurrence in patients with limited stage small cell lung cancer. Initial results of a Canadian Multicenter Randomized Trial. 282 89

Seventy-one patients received adjuvant Cytoxan (cyclophosphamide; Bristol-Myers Co, Evansville, IN), Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and cisplatin (CISCA) chemotherapy between March 1981 and March 1986. Patients received adjuvant CISCA chemotherapy if they had pathological findings that were thought to predict for high likelihood of relapse. These included the presence of resected nodal metastases, extravesicular involvement of tumor, lymphatic/vascular permeation of the primary tumor, or pelvic visceral invasion. Sixty-two patients at a similar high risk for recurrence did not receive adjuvant CISCA chemotherapy because they refused, had medical contraindications to therapy, or were not referred for chemotherapy. Two-hundred six patients had a cystectomy performed during the same study period but had none of the poor prognostic features suggesting a high risk for relapse. Sixty-two percent of the patients receiving adjuvant chemotherapy are alive and disease-free for a mean follow-up of 118 weeks (range, 28 to 310 weeks). A survival advantage exists for the adjuvant-treated patients when compared with those with unfavorable pathological findings who did not receive adjuvant chemotherapy (70% v 37%) (P = .00012): no difference exists in long-term disease-free survival for those with favorable pathological findings (long-term disease-free survival 76%) v those who received adjuvant chemotherapy (70%) (P = .33). Adjuvant CISCA chemotherapy prolongs the disease-free survival of some patients following a cystectomy. Patients who benefitted from adjuvant CISCA chemotherapy included those with resected nodal metastases, extra-vesicular involvement of tumor, and direct invasion of the pelvic viscera. Patients not benefitting from adjuvant CISCA chemotherapy in this analysis included those with lymphatic/vascular invasion in their primary tumor as the sole manifestation of high risk for relapse.
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PMID:Adjuvant cyclophosphamide, doxorubicin, and cisplatin chemotherapy for bladder cancer: an update. 317 26


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