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High-dose platinum consisting of combined carboplatin and cisplatin in previously untreated ovarian cancer patients with residual disease.

A phase II trial of carboplatin, 300 mg/m2 day 1, and cisplatin, 50 mg/m2 days 2 and 3 every 4 weeks for six cycles, was performed in 42 previously untreated patients with residual disease after primary laparotomy. Overall, 79% of patients had primary residual tumor larger than 2 cm. The overall pathologic response rate (pathologic complete response [PCR] plus partial response [PPR]) in 37 evaluable patients was 62%, and in PCRs was 22%. Of the responding patients, 78% had primary residual tumor larger than 2 cm. The toxicity was cumulative but manageable, with thrombocytopenia being the main reason for dose reduction. Dose-limiting nephrotoxicity and neurotoxicity occurred in 22% and 7% of the patients, respectively. Combined high-dose platinum as a "single agent" appears to be as active as combination chemotherapy containing cisplatin, and the treatment is feasible. Further clinical trials of this combination alone or combined with other drugs are warranted.

Adult

Combined high-dose carboplatin and cisplatin, and ifosfamide in previously untreated ovarian cancer patients with residual disease.

Carboplatin 200 mg/m2 day 1, cisplatin 50 mg/m2 days 2 and 3, ifosfamide 1,500 mg/m2 days 1 to 3, and mesna 900 mg/m2 days 1 to 3 every 4 weeks for six cycles were given to 37 previously untreated ovarian cancer patients with residual disease after the primary laparotomy. The median observation time was 17+ months (range, 9+ to 24+ months). Of all the patients, 81% had primary residual disease larger than 2 cm. The overall pathologic response rate (pathologic complete response [PCR] plus partial response [PPR]) in 36 assessable patients was 58%, PCR was 42%. Of the PCR patients, 53% had primary residual tumor larger than 5 cm. The substantial hematologic toxicity was manageable, but also the main reason for dose modifications. During treatment, 92% and 100% of the patients developed WBC and platelet nadir values corresponding to World Health Organization (WHO) grades 3 to 4. Dose-limiting encephalopathy, nephro- and neurotoxicity each occurred in 6% of the patients. The high PCR rate warrants further investigations of combined high-dose platinum and ifosfamide.

Adult

A European Organization for Research and Treatment of Cancer--Genitourinary Group phase 2 study of chemotherapy in stage T3-4N0-XM0 transitional cell cancer of the bladder: evaluation of clinical response.

From 1986 to 1990 the European Organization for Research and Treatment of Cancer--Genitourinary Group conducted a phase 2 trial of neoadjuvant chemotherapy in patients with stage T3-4N0-XM0 transitional cell carcinoma of the bladder. The objectives were to evaluate the clinical response in relation to the pathological response, and to measure the side effects of chemotherapy. Of 171 patients entered 136 were fully evaluable: 18% had clinical complete remissions, 36% had clinical partial remissions, 39% had no clinical remissions and 10% had unknown response. A selected subgroup of 76 patients underwent cystectomy after 2 or 4 courses of chemotherapy: 2 were not evaluable for pathological response because of preoperative radiotherapy after neoadjuvant chemotherapy, 16 had a pathological complete remission, 7 had a pathological partial remission and 51 had no pathological remission. Comparison of the clinical response or T category only after 2 courses of chemotherapy with the pathological response after 2 or 4 courses of chemotherapy showed that in a number of patients the disease status could be downstaged to pathological complete or partial remission by additional courses of chemotherapy. If the discrepancies between clinical and pathological responses, or between T and P categories, induced by further downstaging after additional chemotherapy were left out, it was shown that clinical complete and partial remissions were a heterogeneous group but nonresponders could be delineated with a 100% accuracy by clinical response evaluation and transurethral resection biopsy only. Furthermore it seems important to establish the number of chemotherapy courses to induce a maximal response of the primary tumor.

Adult

Randomized trial in advanced ovarian cancer comparing cisplatin and carboplatin.

The aim of this multicenter randomized trial was to compare carboplatin (400 mg/m2) and cisplatin (100 mg/m2) in patients with untreated advanced epithelial ovarian cancer. Toxicity and treatment efficacy assessed by pathological response rate, progression-free survival, and survival were the endpoints of the study. One hundred seventy-three patients with advanced epithelial ovarian cancer, F.I.G.O. (International Federation of Gynecology and Obstetrics) stage III and IV were accrued in the trial. The median follow-up time was 15 months (maximum, 34); three patients in each treatment arm were not eligible (four, nonepithelial ovarian cancer type; one, no data, and one, stage II). Patient characteristics were similar in the two groups. In the carboplatin-treatment arm, the overall pathological response rate was 57.3% and the complete pathological response rate was 26.8%. In the cisplatin-treatment arm, the overall pathological response rate was 71.6% and the complete pathological response rate was 24.7%. There was no statistical difference in the two arms in survival or progression-free survival. Cisplatin was more nephrotoxic while carboplatin induced a higher degree of myelosuppression, especially thrombocytopenia; however, severe hematological toxicity was seldom observed. Carboplatin is a cisplatin analog with definite activity in ovarian cancer, but it is more active than the parent compound. Because of less nonhematological toxicity, carboplatin is undoubtedly a useful substitute in patients who cannot be given cisplatin. Further experience is needed to indicate whether or not carboplatin should completely displace cisplatin in the clinical treatment of ovarian cancer.

Adult

Autonomic disturbances and cardiovascular reflexes in idiopathic Parkinson's disease.

A total of 22 patients suffering from idiopathic Parkinson's disease and 20 age-matched volunteers were questioned about autonomic disturbances and all underwent four non-invasive tests examining cardiovascular reflexes. Significantly more autonomic disturbances were reported by the patients than by the controls. Resting blood pressure was significantly decreased in patients taking dopamine agonists, whereas it was normal in those patients who only received levodopa and anticholinergics. Resting heart rate and resting beat-to-beat variation were normal in the patients, as were the blood pressure response to standing and the postural heart rate response. No pathological response to the Valsalva manoeuvre could be detected. On the other hand, the heart rate variation evoked by deep breathing as well as the blood pressure response and the heart rate response to sustained isometric exercise were significantly diminished in the patients with idiopathic Parkinson's disease. These findings indicate a central disturbance of cardiovascular reflex control, whereas the corresponding peripheral pathways seem to be normal.

Aged

Neoadjuvant treatment of stages T2 to T4 bladder cancer with cis-platinum, cyclophosphamide and doxorubicin.

In an ongoing phase II study 17 patients with potentially operable transitional cell carcinoma of the bladder (stages T2 to T4, Nx, Mo) have been treated with intravenous cis-platinum (50 mg.per m.2), cyclophosphamide (400 mg.per m.2) and doxorubicin (40 mg.per m.2). They were to receive 3 treatments at 3-week intervals before cystectomy and 2 treatments at 3-week intervals commencing 5 weeks after cystectomy. Of 17 patients 14 (82 per cent) completed all 3 preoperative treatments but only 7 (41 per cent) continued on to complete the entire 5 treatments. In most cases incomplete therapy was due to patient refusal. Toxicity was low as measured by World Health Organization standards. Of the 17 patients 9 (53 per cent) exhibited objective tumor response (pathological downstaging or greater than 50 per cent reduction of tumor volume determined by either computerized tomography scan and/or endoscopic examination. When the determination was made by endoscopy the changes were dramatic and not borderline.) No patient demonstrated a pathological complete response. All 9 of the responders (100 per cent) remain clinically free of disease at a median follow-up of 19 months (range 4 to 30 months). The 8 nonresponders have done poorly with 5 dead of disease, 1 alive with pelvic recurrence and 2 free of disease at 4 and 12 months. These tumor response rates compare favorably with other cis-platinum-based combination regimens. The response to the chemotherapy appears to be an important prognostic indicator. Phase III trials must be conducted to determine whether this neoadjuvant chemotherapy regimen has a significant effect on long-term patient survival.

Aged

Respiratory irritation from environmental tobacco smoke.

Acute physiological and chronic pathological responses of the respiratory tract to environmental tobacco smoke (ETS) are reviewed briefly. This study excludes discussion of the possible risk of lung cancer and the known impact of carbon monoxide on the fetus and adult. In some environments, the dose of particulate matter and the concentrations of irritant vapors absorbed on the ETS particles reach a level for which a physiological response may be expected, not only in the nose but also the bronchi. However, direct measurements indicate only small increases of nasal and bronchial resistance if normal subjects are exposed to maximal, likely concentrations of ETS. ETS is readily detected by the nonsmoker, but there is no strong evidence that pulmonary reactions have a psychogenic basis. The condition of approximately 20% of asthmatic patients is exacerbated by ETS exposure. Further study is needed to clarify the likelihood that adults will progress from a minor physiological response to pathological reactions, e.g., chronic obstructive lung disease. In young children (who are less able to escape from ETS), the association between exposure and an increase in respiratory disease is stronger than in adults. Exacerbation of asthma and an increase of respiratory disease are further arguments for legislation to guarantee smoke-free air to the nonsmoking public.

Asthma

Exercise and pathologic complete response to cancer treatment: a systematic review and meta-analysis.

PURPOSE: Neoadjuvant chemotherapy (NACT) is a commonly recommended approach for treating several cancers, and improving patients' outcomes to this therapy is important. This systematic review and meta-analysis assessed the impact of exercise on pathologic complete response (pCR), a key short-term marker of treatment efficacy, in patients with solid tumors receiving NACT. METHODS: Four electronic databases were searched for randomized controlled trials with physical exercise during NACT as an intervention published until May 2025. Risk of bias was assessed using Cochrane RoB 2.0 and the TESTEX scale. A random-effect meta-analysis using the inverse variance method synthesized the results. Heterogeneity was assessed using I2 and chi2 statistics. Risk ratio estimated the effect size. RESULTS: Eight studies involving 504 patients with breast, esophageal, gastric, or rectal cancer were included in the final analysis. Exercise interventions consisted of aerobic and resistance exercise. Overall, there were no significant differences between exercise and control groups in the rate of pCR to NACT (pooled risk ratio: 1.08 (95% CI: 0.82 to 1.43) Z = 0.56, p = 0.58). However, meta-regression data from breast cancer (BC) studies (4 studies, 367 participants) suggest exercise may be associated with enhanced tumor response to NACT in HR + /HER2- subtypes (regression coefficient: 0.83 (95% CI: -0.00 to 1.67), p = 0.05). CONCLUSION: Exercise during NACT did not improve pCR across cancer types. Exploratory meta-regression findings suggest a possible benefit of exercise in BC patients with the HR + /HER2- subtype. These results should be interpreted with caution due to the small number of studies and low certainty of the evidence.

Humans

A phase I-II trial of intraperitoneal cisplatin and alpha-interferon in patients with persistent epithelial ovarian cancer.

A toxicity, dose, and schedule study of intraperitoneal (ip) cisplatin and alpha-interferon was conducted as a salvage therapy for patients with persistent, advanced epithelial ovarian cancer after primary systemic therapy with cisplatin-combination chemotherapy. Twenty-four patients were entered into this prospective, nonrandomized phase I-II trial conducted at two institutions following a uniform protocol. Cisplatin doses were escalated from 45 to 90 mg/m2, and alpha-interferon doses were escalated from 10 to 50 x 10(6) IU. At protocol entry, 4 (16%) patients had microscopic residual disease at second-look laparotomy, 5 (21%) had minimal residual disease less than 5 mm, 7 (30%) had residual disease 5-20 mm, and 8 (33%) had bulky residual disease greater than 20 mm. Toxicity was acceptable overall. Hematopoietic toxicity included a grade 3 total white cell count in 12% of courses when the cisplatin dose was equal to or greater than 60 mg/m2. Renal toxicity was modest with grade 2 toxicity in 20% of courses with a cisplatin dose greater than 60 mg/m2. Gastrointestinal toxicity, especially nausea and vomiting was seen in most courses; however, it was grade 3 and dose-limiting in greater than 30% of courses with cisplatin 75-90 mg/m2. General malaise, fever, flu-like symptoms, chills, and myalgias were seen in most courses, but it was dose-limiting (grade 3) toxicity in 6-11% of cycles when the dose of interferon was 25-50 x 10(6) IU. There was no grade 4 toxicity. Thus, the maximum tolerated dose (MTD) of the combination is 60 mg/m2 cisplatin and 25 x 10(6) IU interferon. Eighteen patients were evaluable for response, 15 of whom had responded to prior cisplatin therapy and 3 had not. Of the 10 patients evaluable for clinical response, one patient (10%) achieved a complete response (CCR), and one (10%) had a partial response (PCR). The progression free interval (PFI) and survival were 11 months and 19 months, respectively, for the CCR patient, 6 and 11 months, respectively, for the PCR patient, and the mean survival for nonresponders was 8 months. The other 8 patients underwent a reassessment laparotomy: 2 (25%) achieved a complete pathologic response (CPR), and 3 (38%) had a partial pathologic response (PPR). Both pathologic responses were in patients with minimal residual disease less than 5 mm.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult

The cardiac hypertrophic responses to pathologic and physiologic loads.

Myocardial hypertrophy is an adaptive response of the heart to an imposed load. Two distinct patterns of hypertrophy are discussed, pathologic and physiologic, which differ in their mechanical and biochemical features. Evidence is presented that supports the following hypotheses: the nature of the hypertrophy reflects the nature of the stimulus; the function of the hypertrophied heart reflects its biochemistry; and the degree of responsiveness of the heart varies with species and with age.

Animals

Salt and water control at altitude.

The physiological effect of altitude hypoxia, in the absence of exercise, is a sodium and water diuresis with decrease in plasma and extra-cellular volumes. Plasma aldosterone concentrations (PAC) are reduced but plasma atrial natriuretic peptide (ANP) levels are modestly increased. Day-long exercise at low altitude has almost opposite effects on fluid balance. There is an anti-diuresis, sodium retention, expansion of the plasma and extra-cellular compartments, elevation of PAC and ANP. Subjects who develop acute mountain sickness (AMS) show a pathological response to hypoxia even before the development of symptoms. There is an anti-diuresis, sodium retention, increased plasma and extra-cellular volumes and increased PAC compared with subjects resistant to AMS. Plasma ANP tends to be elevated compared with sea level values but the relation of ANP levels to AMS is variable. In general therefore, the pathological response to altitude hypoxia parallels that of exercise at low altitude and is opposite to the physiological response. Both exercise and the pathological response predispose the subject to edema and are probably important in the genesis of AMS.

Acute Disease

The influence of cytoreductive surgery on progression-free interval and survival in epithelial ovarian cancer.

In 1980, Dr George E. Moore published an editorial in Surgery, Gynecology and Obstetrics entitled 'Debunking debulking'. He included advanced ovarian cancer in his personal list of 'faulty' debulking procedures. Some of hist statements have merit. He contends that overly aggressive procedures that leave microscopic tumour cells that will soon grow and kill the patient are unindicated. He further points out that one cubic centimetre of tumour will contain approximately a billion cells. However, there are factors in ovarian cancer that should cause one to take exception to Dr Moore's statement. First, there is good evidence that the use of cisplatin-based multidrug chemotherapy may eradicate microscopic tumour deposits in a significant number of patients. Secondly, even multiple aggregates of tumour with a billion or more cancer cells can be eradicated in some cases, and in others can be reduced sufficiently to allow significant palliation. In evaluating the information which has been reviewed in this discussion of cytoreductive surgery for advanced ovarian cancer, it is apparent that cytoreductive surgery is not only indicated, but mandated in many facets of the management of ovarian cancer. The following principles seem to be supported by the existing literature: 1. Current diagnostic techniques do not enable us to diagnose ovarian cancer while still confined to the ovary. Therefore, in the immediate future we will still encounter a large number of patients with advanced disease. 2. The number of complete clinical responses and the number of complete pathological responses (negative second-look surgical reassessments) are greatest in those patients who begin adjunctive therapy with minimal residual disease. 3. Median duration of survival is longer, and long-term survival more likely, in those patients giving complete clinical or complete pathological responses. 4. Some patients appear to benefit from secondary cytoreductive surgery. However, at the present time, evidence of benefit from secondary cytoreductive surgery appears to be limited to those patients who have responded to adjunctive therapy and are found to have residual disease at surgical reassessment. There is no good evidence to support secondary cytoreductive surgery as an 'interval' procedure or its use in patients with progression on primary adjunctive therapy. This development of better chemotherapy regimens, such as cisplatin-based chemotherapy, has resulted in a greater need for effective primary cytoreductive surgery as it is apparent that, on utilizing these new regimens, better results are obtained in patients with minimal residual disease.(ABSTRACT TRUNCATED AT 400 WORDS)

Carcinoma

Pathologic complete response of advanced ovarian mixed mesodermal tumor to cisplatin, adriamycin and dacarbazine: a case report.

Presented is a case report of a stage IIIC primary ovarian mixed mesodermal tumor with gross residual disease following aggressive cytoreductive surgery. Following twelve courses of Cisplatin, Adriamycin and Dacarbazine, second-look laparotomy confirmed a pathologic complete response. The patient is now free of disease at 17+ months.

Antineoplastic Combined Chemotherapy Protocols

Vaccination studies against experimental bovine Pasteurella pneumonia.

Vaccination-challenge experiments were conducted in colostrum-deprived calves to evaluate the efficacy of Pasteurella bacterins and vaccines against experimental pneumonic pasteurellosis. Calves were vaccinated with formalin-killed bacterins and live vaccines, then challenge exposed intratracheally with P. haemolytica or P. multocida. Infectious bovine rhinotracheitis virus was inoculated intranasally three to four days prior to P. haemolytica challenge-exposure. All calves were examined for macroscopic and microscopic lesions after being found dead or following euthanasia four to seven days after challenge exposure with the bacterial pathogen. Clinical, hematological, and pathological responses to challenge exposure in aluminum hydroxide absorbed P. haemolytica and P. multocida bacterin-treated calves were consistent with the pneumonic lesions of pulmonary pasteurellosis in the control calves. An oil-adjuvanted P. haemolytica bacterin limited clinical and pathological responses in the affected calves whereas a P. multocida oil-adjuvanted bacterin did not. Both clinical and pathological responses to challenge exposure in calves vaccinated with live Pasteurella vaccines were less severe than those of the control calves. Vaccine effectiveness appeared to be dose dependent.

Animals

A preliminary report of combination chemotherapy with cisplatin and mitomycin-C followed by radical hysterectomy or radiation therapy in patients with locally advanced cervical cancer.

Neoadjuvant chemotherapy with cisplatin and mitomycin-C was used in the primary treatment of 17 patients with locally advanced cervical cancer (stages Ib-IIIb; tumor diameter greater than 5 cm) prior to definitive local treatment with radical hysterectomy or radiotherapy. Thirteen of the seventeen patients (76.5%) responded to initial chemotherapy, permitting a radical hysterectomy in ten patients. At histologic examination of the surgically resected primary tumor and lymph nodes, complete pathologic responses were found in 2 patients and partial pathologic responses in 8 patients. The median follow-up time is 14.5 months with a median survival for all patients of 52 weeks. All responders are alive. No therapy-related deaths, major complications, or delay in treatment occurred. Neoadjuvant chemotherapy with mitomycin-C and cisplatin is feasible and may be of benefit for patients with locally advanced cervical cancer.

Adult

The prognostic and therapeutic value of second-look laparotomy in advanced ovarian cancer.

Of 267 patients with ovarian cancer FIGO stages III and IV, 157 underwent second-look laparotomy after combination chemotherapy consisting of cis-platinum and cyclophosphamide with and without doxorubicin. At second-look operation 45% had macroscopic tumour, 15% microscopic tumour, and 40% complete pathological response. Survival 3 years after second look was: complete pathological response 74%; microscopic disease 24%; visible tumour less than 1 cm 28%; visible tumour greater than 1 cm 17%; negative cytology 59%; and positive cytology 18%. Of the patients with macroscopic tumour, 29% had all visible tumour removed at second look. Three-year survival for these patients was about 45%.

Antineoplastic Combined Chemotherapy Protocols