Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0032285 (pneumonia)
 54,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Seventeen patients were entered into a Phase I/II trial of concurrent hyperfractionated radiation therapy (7,440 cGy total dose; 120 cGy b.i.d.) combined with constant infusion of 5-fluorouracil (5-FU) (1,000 mg/m2/24 hours for 72 hours) and cisplatin (DDP) (50 mg/m2) for a total of three cycles. Thirteen patients had Stage IV disease; three, Stage III disease; and one, Stage II hypopharyngeal disease. Thirteen of 17 patients had positive cervical lymph nodes, and the mean size of the largest lymph node was 5.5 x 5.1 cm. The patients were not treated with planned adjunctive surgery except for one patient who had a radical neck dissection for massive, rapidly growing cervical adenopathy, which recurred promptly within 1 month before the initiation of protocol therapy. After the initial six patients were entered, mitomycin-C (Mito 8 mg/m2) was added during the second cycle. All the patients completed the planned course of radiotherapy with a median dose of 7,440 cGy and a mean dose of 7,248 cGy except for two patients who died--one from toxicity and the other, suicide. The predominant toxicity was mucositis, which was grade 3/4 in 11 of 15 patients, resulting in an average interruption of radiation therapy of 12 days. Weight loss was significant and was on the average 12% of baseline weight. Hematological toxicity was mild in the 5-FU/DDP group (only one grade 3 toxicity of six) and severe in the 5-FU/DDP/Mito-treated patients (five of eight patients having grade 3/4 toxicity including one leukopenic pneumonitis death). Additional toxicity included one parapharyngeal cellulitis, which responded to antibiotics. Noncompliance with the complex regimen was only seen in three patients. One patient refused b.i.d. radiation therapy, and one patient refused further chemotherapy after the first cycle. Additionally, one patient who had a severe ethanol withdrawal reaction during the first cycle of 5-FU/DDP did not receive further chemotherapy. The complete response rate of both primary site and neck by the protocol regimen alone was 71%. However, two patients, one from each group, did undergo salvage neck dissection, and the locoregional control is currently 73%, with a mean follow-up time of 18.4 months. The feasibility of combining hyperfractionated radiation therapy with aggressive concurrent chemotherapy was demonstrated. The response and local control rate justifies the added toxicity of concurrent chemotherapy and radiation therapy.
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PMID:Hyperfractionated radiation therapy and concurrent 5-fluorouracil, cisplatin and mitomycin-C in head and neck carcinoma. A pilot study. 159 Feb 80

Cytotoxic drugs were administered either in single or fractionated doses before, during, or after a standard course of 5 daily X ray exposures. SCCVII and RIF-1 tumors were grown from cells implanted in the gastrocnemius muscles of syngeneic C3H/Km mice, and treatments were evaluated by regrowth delay (GD). Non-tumor-bearing mice were irradiated locally to the upper abdomen for analysis of intestinal crypt cell survival, an acute normal tissue effect; other non-tumor-bearing mice were irradiated locally to the thorax for analysis of early (pneumonitis) and late (fibrosis) effects on the lungs, as reflected in changes in breathing rates. In a series of experiments to test the combination of i.p. 5-FU, cis-DDP, and X ray, dose effect factors (DEF's) were compared so that therapeutic gain factors (TGF's) could be calculated from the ratio, DEF (tumor)/DEF (normal tissue). The highest TGF, 6.7 (tumor/duodenum), was obtained for the schedule in which 100 mg/kg 5-FU was given 24 hr before the simultaneous administration of 1.6 mg/kg cis-DDP and X ray for 5 consecutive days. The following summary refers only to tumor growth delay data. In confirmation of previous extensive experiments, the combination of cis-DDP + X ray showed supra-additivity, whether the drug was given in a single dose (abbreviated P) or simultaneously with X ray (abbreviated px), that is, P x x x x x or px px px px px. For CY + X ray, the greatest supra-additivity was obtained for either C x x x x x or x x x x x C. 5-FU alone did not act supra-additively with fractionated irradiation, but the addition of 5-FU to cis-DDP + X ray was supra-additive for certain schedules, maximally for F px px px px px. CY combined to give greater than additivity with either cis-DDP or X ray alone, and the combination of CY + cis-DDP + X ray appeared to be supra-additive for five different schedules, maximally for C x x x x x P. Normal tissue effects are being evaluated for these same schedules so that TGF's might soon be obtained.
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PMID:Schedule-dependent therapeutic gain from the combination of fractionated irradiation plus c-DDP and 5-FU or plus c-DDP and cyclophosphamide in C3H/Km mouse model systems. 199 83

Response to chemotherapy and survival was retrospectively analyzed in 28 patients with bulky retroperitoneal and disseminated seminoma treated between 1977 and 1983. The median age was 41 years (range: 23-52). All patients had histological evidence of pure testicular seminoma, however, 14 patients revealed moderate increases of human beta-chorionic gonadotropin levels. Prior radiotherapy had been given to 9/28 (32%) patients. Treatment consisted of at least four courses of simultaneous or sequentially alternating therapy with cisplatin, vinblastine, bleomycin plus/minus adriamycin (PVB +/- A), administration of ifosfamide or combination therapy with ifosfamide/cisplatin (IFS/DDP) or ifosfamide/etoposide (IFS/ETP). Twenty-five of 28 patients (89%) achieved a complete (CR), and 3/28 patients a partial remission. Relapse occurred in 1/8 CR patients after adjuvant postchemotherapeutic irradiation, and in 1/11 patients without any further radiotherapy. So far, 23/28 patients (82%) are free of disease after a median follow-up of 28+ (14+----82+) months. Marked myelosuppression was observed in previously irradiated patients, mainly after PVB +/- A therapy. In two patients, transient nephrotoxicity developed after PVB and IFS/DDP, respectively. After PVB +/- A chemotherapy, three patients revealed polyneuropathy, paralytic subileus and bleomycin-induced pneumonitis, respectively. In conclusion, the present series suggests a high probability of continuous CR in even bulky retroperitoneal and widespread metastatic seminoma. So far, no definite conclusions can be made on the therapeutic superiority of one of the different chemotherapeutic regimens used. However, this preliminary experience suggests that the combination of ifosfamide and etoposide or cisplatin may prove less toxic than sequentially alternating or simultaneous PVB +/- A chemotherapy.
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PMID:Chemotherapy of metastatic seminoma. 257 65

Synchronously administered cis-platinum (cis-DDP) and radiation therapy have been used to treat unresectable squamous cell carcinomas of the head and neck. The purpose of this study was to evaluate the efficacy and tolerance of preoperative adjuvant cis-DDP plus radiation therapy in operable stage III and IV head and neck cancers. Radiation therapy (4,500 rad) was delivered in 180-rad daily fractions. Cis-DDP (20 mg/M2) was given before radiotherapy on days 1-4 and 21-24. Eighteen patients began therapy; 16 completed the combined regimen. Toxicity included stomatitis and WBC below 2,500/mm3. One patient died from therapy of a cerebrovascular accident. Sixteen patients (89%) achieved a complete or partial response to therapy. Complete responses were observed in 13 of 18 primary tumors (72%), and in all three patients with cervical lymphadenopathy. Complete responses were noted for lesions of the nasopharynx, oral cavity, pharynx, hypopharynx, and larynx, for all histologic grades of squamous cell carcinoma. Twelve patients underwent curative surgery. Site-related morbidity occurred in two patients (15%) and a third patient developed postoperative pneumonia. Five of 10 resected primary tumors with preoperative complete responses were pathologically negative for tumor. Concurrent bolus cis-DDP and radiation therapy are well-tolerated and result in impressive tumor reduction. Morbidity after subsequent curative surgery is low, and histologic complete responses are frequent.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Preoperative simultaneously administered cis-platinum plus radiation therapy for advanced squamous cell carcinoma of the head and neck. 374 47

Treatment results of advanced soft tissue sarcomas are still suboptimal. To evaluate the clinical effects of a combination therapy (FADIP) with Adriamycin (ADM), ifosfamide (IFO), cisplatin (DDP) plus continuous infusion of 5-fluorouracil (FU) as a synergistic factor for alkylating agents, a phase II study was initiated in patients with advanced soft tissue sarcomas of different histological subtypes. Fifty-six previously untreated patients with advanced soft tissue sarcomas of different histological subtypes (24 females, 31 males, median age 51.3 years, median Karnofsky performance status 80%) were included in this study. Treatment consisted of ADM 50 mg/m2 i.v. on day 1, IFO 4,000 mg/m2 i.v. on day 1, mesna 800 mg/m2 i.v. 3 x with 8-hour intervals on day 1 starting with IFO administration, FU 500 mg/m2 i.v. as 24-hour infusion on days 1 + 2, DDP 100 mg/m2 i.v. on day 2. This regimen was repeated every 4 weeks for at least 2 cycles. Major WHO grade III/IV hematological toxicity was observed in 35/56 patients. One toxic death due to severe neutropenia and fungal pneumonia occurred. Granulocyte colony-stimulating factor was administered in 8/35 neutropenic patients. Time to recovery was significantly reduced and no infectious complication was observed. WHO grade III/IV toxic diarrhea was observed in 8 patients requiring intravenous fluid replacement. WHO grade III/IV nausea occurred in 11 patients, 9/11 responded to symptomatic treatment with ondansetron alone. The overall response rate was 30.3%. The median duration of response (complete/partial response, CR/PR) was 18.1 months, the median progression-free interval was 4.5 months. The median survival time of all patients was 11.8 months, and 18.1 months in responding patients (CR/PR). Tumor-related pain was effectively reduced in 15/31 patients under treatment. FADIP produces comparable response rates to other standard treatment regimens in soft tissue sarcomas. Prolonged duration of response and median survival may be due to the use of continuous infusion of FU as a synergistic factor to alkylating agents. Granulocyte colony-stimulating factor is effective in reducing the otherwise observed high rate of WHO grade III/IV hematological toxicity with severe neutropenia.
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PMID:Combination of 5-fluorouracil, adriamycin, ifosfamide and cisplatin in metastatic adult soft tissue sarcoma: results of a phase II study. 857 Jan 33