Can fenretinide protect women against ovarian cancer?
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Female↗
Biomedical subjects
V Fosser
Publications and source records attributed to V Fosser.
Pharmacokinetics and tumor concentration of intraarterial and intravenous cisplatin in patients with head and neck squamous cancer.
Tumor-tissue platinum levels and major pharmacokinetic parameters were determined in 11 patients with head and neck squamous cancer (HNSC) who were given cisplatin (50 mg/m2 daily x 2 days) and 5-fluorouracil (5-FU; 1000 mg/m2, continuous infusion x 5 days) either i.a. or i.v. The plasma peak platinum concentrations (cmax) and the areas under the curve for total platinum concentration versus time (AUC) during i.a. infusions were lower than the i.v. cmax (mean, 1.92 +/- 0.28 and 4.08 +/- 2.80 mg/l, for i.a. and i.v. infusions, respectively) and AUC values (mean, 22.55 +/- 4.96 and 40.66 +/- 10.71 mg h-1 l-1 for i.a. and i.v. treatment, respectively), suggesting a first-passage extraction of the drug by the tumor mass during i.a. infusion. However, no statistically significant difference was found in platinum tumor concentrations after i.a. administration versus i.v. infusion. The lack of a difference in tumor platinum concentrations between the i.a. and the i.v. administration routes might be explained either by a relatively high blood supply to the tumor area, enabling efflux of the surplus free platinum from the tissue, or by the delay between drug infusion and biopsy. After three cycles of i.a. treatment good tumor remission was obtained with minimal local toxicity. Larger clinical studies testing the advantages of the i.a. administration route over i.v. infusion appear to be necessary.
Adult↗
Oral ondansetron (GR 38032F) for the control of CMF-induced emesis in the outpatient.
The efficacy of the serotonin antagonist ondansetron (GR 38032F) was evaluated in the prevention of nausea and vomiting induced by CMF chemotherapy in 29 breast cancer patients. At their first treatment course of CMF, all given IV on day 1 q 21 days, patients were given oral antiemetic treatment as follows: ondansetron 8 mg, 2 h prior to CMF, repeated after 5 and 10 h the day of chemotherapy and then 8 mg tds for a minimum of 3 days to a maximum of 5 days following chemotherapy. At first course of CMF, complete protection from emesis and nausea was observed in 86.2% and 62% of patients, respectively. At subsequent CMF courses with ondansetron, complete control of emesis was observed in 80% of patients. Side effects were mild and no dystonic reactions were observed. Ondansetron represents an effective, safe, and easily administered outpatient regimen. The addition of a corticosteroid to ondansetron could further improve control of CMF-induced emesis.
Administration, Oral↗
LH-RH analogue Zoladex in the treatment of pre- and perimenopausal women with metastatic breast cancer (results of the Italian Cooperative Study).
From May 1987 to May 1989 sixty one pre- and perimenopausal women with advanced or recurrent breast cancer entered in an open non comparative study. They were treated, as a first-line therapy, with goserelin (Zoladex ICI-118630) a long acting gonadotropin-releasing hormone (LH-RH)-analogue in a depot formulation. Fifty three patients were evaluable for response; median age at entry was 41 years (range 28-56). Serum concentrations of 17 beta estradiol, LH and FSH were significantly suppressed within the first four weeks of therapy and remained suppressed for the whole duration of treatment. Subjective responses were observed, such as pain reduction and/or performance status improvement in 58% of patients. Overall objective response (CR + PR) occurred in 16 (30.2%) patients in all major sites of disease with a median time to response of 12 weeks (range 8 to 48 weeks) and a lifetable median duration of response of 36 weeks (range 16 to 76 weeks). The lifetable median time to progression was 17 weeks (range 5 to 76 weeks). Goserelin depot was well tolerated with no withdrawal due to possible adverse reactions. The observed subjective and objective response rates are comparable to those induced by surgical oophorectomy. Goserelin provides a well tolerated medical alternative to ovarian ablation, without the morbidity associated to surgery. In conclusion the present paper suggests that this innovative chemical estrogen deprivation, in premenopausal breast cancer patients, might be favorably investigated as an adjuvant therapy in future clinical trials.
Adult↗
Leucovorin calcium enhancement of mucositis after continuous infusion fluorouracil and short infusion cisplatin.
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Aged↗
Systemic chemotherapy with cisplatin, 5-fluorouracil and allopurinol in the management of advanced epidermoid esophageal cancer.
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Adult↗
Phase III randomized study of fluorouracil, epirubicin, and cyclophosphamide v fluorouracil, doxorubicin, and cyclophosphamide in advanced breast cancer: an Italian multicentre trial.
From February 1983 to January 1985, 497 patients with advanced breast cancer were randomly allocated to receive either epirubicin or doxorubicin in the following combination chemotherapy regimen: fluorouracil (5-FU) 500 mg/m2 intravenous (IV) on days 1 and 8; epirubicin or doxorubicin 50 mg/m2 IV on day 1; cyclophosphamide 500 mg/m2 IV on day 1 (FEC or FAC). Cycles were repeated every 21 days until progression or to cumulative doses of 700 mg/m2 for epirubicin and 550 mg/m2 for doxorubicin. Dose reductions were applied according to the standard criteria. Activity was evaluated in 443 patients (222 in the FEC arm and 221 in the FAC arm). The two experimental groups were comparable in age, performance status, menopausal status, histology, previous treatments, and site of the disease. The overall response rate (complete response and partial response [CR + PR]) was not significantly different: 53.6% for FEC and 56.5% for FAC. The median time to progression was 273 days for FEC and 314 days for FAC; the median survival time was 591 and 613 days, respectively. Leukopenia, anemia, nausea, and vomiting were significantly lower in patients treated with FEC. As for cardiotoxicity, four cases of congestive heart failure (CHF) were recorded among patients treated with FAC while only one was observed in the FEC group. These results indicate that epirubicin in a combination chemotherapy regimen is as active as doxorubicin and is significantly less toxic.
Adult↗
High-dose medroxyprogesterone in disseminated breast cancer. Correlation between bioavailability and clinical response.
Clinical response to high-dose medroxyprogesterone (MPA), administered following three different routes of administration (i.m., p.o. + i.m., p.o.) and monitoring drug plasma levels, was evaluated in pretreated advanced breast cancer patients. Fifty-eight of 68 eligible patients were considered evaluable for response. Age ranged between 36 years and 82 years. Fifty-six of 58 evaluable patients were postmenopausal. An overall remission rate of 48% was achieved with i.m. MPA, 50% with combined (i.m. + p.o.) modalities; only a 19% remission rate was recorded in the p.o. group. Response rate and MPA plasma concentrations were correlated, and a drug level of 80 ng/ml, by means of a GLC method, seems to identify a subset of patients with high probability of response. Only mild toxic effects were recorded.
Adult↗
Phase II study of cisplatin, 5-FU, and allopurinol in advanced esophageal cancer.
Forty patients with advanced squamous cell carcinoma of the esophagus were treated with a combination of cisplatin, 5-FU (by continuous 5-day infusion), and allopurinol; 37 are evaluable for response. Thirteen remissions (35%) were obtained, including three complete and ten partial, with a median duration of 9 months. After chemotherapy, seven responding patients underwent a surgical procedure, which was radical in four. The most frequent side effects were nausea and vomiting. This regimen is effective and can be included in a multimodality approach.
Adult↗
Peptichemio in pretreated patients with ovarian cancer.
From January 1978 to October 1982, 47 patients with histological diagnosis of epithelial cancer of the ovary received peptichemio (PTC) at a dose of 70 mg/m2 (maximum, 120 mg total) every 15 days. Forty-two patients are now evaluable: 27 with stage III and 15 with stage IV disease. All patients but four with stage IV disease had been pretreated and had received at least one drug combination (median, three drugs per patient, including alkylating agents). Before the administration of PTC, the tumor extension in the abdomen was carefully assessed in all patients: ten patients had residual tumor less than 2 cm in diameter, while 32 patients had tumor greater than 2 cm in diameter. Objective responses were obtained in ten patients (23.8%): six complete remissions and one partial remission were observed in stage III patients and one complete remission and two partial remissions were observed in stage IV patients. Of the ten responding patients, eight had tumors less than 2 cm in diameter before receiving PTC. The median duration of response was 16 months. The most frequent side effects were myelosuppression and phlebosclerosis. Bone marrow depression was a common finding after the third course in heavily pretreated patients. Accordingly, in these patients a schedule interval of 3 weeks should be more appropriate. Since most of the responders were in the "small tumor" category, PTC appears to be an active drug in patients with ovarian cancer having small tumors (less than 2 cm). On the other hand, the response rate in a nonselected population of patients remains to be clearly defined with further studies.
Adult↗
MPA plasma levels after oral administration in gastrectomized cancer patients during chemotherapy.
Five patients (3 females; 2 males) who underwent gastrectomy for carcinoma were administered adjuvant chemotherapy and high dose medroxyprogesterone acetate (HD-MPA) as supportive therapy. MPA administered p.o. was regularly absorbed; the drug was well tolerated and was almost lacking in toxicity. MPA, thanks to its myeloprotective activity and its anabolic effects, can be used as supportive therapy in the treatment of a wide range of malignancies.
Adenocarcinoma↗
FAM2 regimen in disseminated gastric cancer.
Forty-four previously untreated patients with advanced inoperable and/or disseminated gastric carcinoma were given an i.v. combination (FAM2) chemotherapy of 5-fluorouracil, 400 mg/m2 on days 1, 2 and 3, and 21, 22 and 23; adriamycin, 40 mg/m2 on days 2 and 22; and mitomycin C, 10 mg/m2 on day 1, with a recycle on day 42 (1 cycle = 41 days). Forty patients have completed 2 cycles and are evaluable (median number of cycles 5; range 3 to 8): 26 of these achieved a partial remission, with a response rate of 65%; 4 (10%) gained a stable situation for 3 to 6 months, and 10 (25%) showed progression of disease. Median duration of partial remissions was 10 months, and median survival was 15 months for responders and 5 months for nonresponders. A fall in WBC (less than 2500/microliter) occurred in 7% and of platelets (less than 80,000/microliter) in 4.5%. Total alopecia occurred in 20 of 40 patients and nausea and or weakness were common findings. No drug-related infection, bleeding or death was observed. Patients with advanced gastric carcinoma can derive useful palliation from FAM2 chemotherapy.
Adult↗
Cisplatin, bleomycin and methotrexate in the treatment of advanced oesophageal cancer.
From February 1981 to September 1982, 34 patients with metastatic or locally advanced (inoperable) epidermoid carcinoma of the oesophagus were treated with a combination of cisplatin, bleomycin and methotrexate. Thirty-one patients are now evaluable for response: 16 of 31 (52%) experienced some improvement, but only eight (26%) obtained major responses (one complete and seven partial). Responses were obtained rapidly within the first two courses. The median duration of responses was 5 months. The median survival from start of therapy was 8 months for responsive and 5 months for non-responsive patients. Gastrointestinal toxicity (cisplatin-related) and mild myelosuppression were the most prominent side-effects. This combination chemotherapy proved to be only of small efficacy in the long-term control of advanced oesophageal cancer. However, because the responses were obtained rapidly, it is conceivable that a similar regimen (with increased dosage of cisplatin) applied before surgery to patients with limited disease could obtain a reduction of the bulky tumour, with a possible increase of the resectability rate and destruction of micrometastases.
Adult↗
Treatment of multiple myeloma with M-2 protocol and without maintenance therapy.
From September 1975 to December 1981, 63 consecutive untreated patients with multiple myeloma received the Lee M-2 protocol. We used the same drugs (melphalan, cyclophosphamide, vincristine, BCNU and prednisone) but employed the lowest suggested doses and recycled earlier, i.e. after 21-28 days. Thirty-five patients (62.5%) were in stage III, 16 (28.6%) in stage II and 5 (8.9%) in stage I. An objective response (reduction in paraprotein production rate greater than 50%) was obtained in 44 out of 56 cases (78%); 32 (57%) had a reduction greater than 75%. The median duration of response was 21.5 months. In responding patients the treatment was stopped after 1 yr and resumed only at relapse. Twenty-two out of 25 retreated patients are now evaluable. Eighteen of them (82%) responded again; in retreatment the degree of response was lower, but the duration of second response was only slightly lower than the first response (15.7 vs 21.5 months, NS). Of 7 patients receiving a third M-2 reinduction 4 responded again. The median survival for all the patients is 51 months. The high rate of second response to the M-2 regimen after an unmaintained remission brings into question the value of continuous therapy in responsive multiple myeloma.
Adult↗
Serum lactate dehydrogenase (LDH) as a prognostic index for non-Hodgkin's lymphoma.
According to pretreatment values of serum lactate dehydrogenase (LDH), 113 consecutive patients with non-Hodgkin's lymphoma were divided into three levels: level 1 (within normal range) with LDH less than 250 U/l; level 2 (moderately increased) with LDH between 250 and 500 U/l; level 3 (highly increased) with LDH more than 500 U/l. LDH was elevated in 46 of 113 patients (41%). Normal values of LDH were associated with a better response to therapy and a longer survival, independent of histological type and clinical stage, with one exception; in stage IV patients conclusions could not be drawn concerning the response to therapy (complete remission occurred only in 8 of 44). Even though level 2 patients behaved slightly better than level 3 patients, no statistical difference has been observed between the two levels. Accordingly, serum LDH can be considered a useful predictor of response to therapy and of survival in non-Hodgkin's lymphoma.
Adolescent↗
A planned prospective study of combined treatment in stage III epithelial ovarian cancer.
In a planned prospective study 39 consecutive patients with stage III ovarian cancer have been admitted in two years. All patients have received initial extensive surgery followed on as out patients basis by 5 courses of A-Cy chemotherapy and by a second operation and further non cross resistant chemotherapy with Platinum, Hexamethyl-Melamine, Polymelphalan; 24 have been found pathologically free of disease at second surgery, and 34/39 are clinically free of disease while reporting. These data, exactly collected and evaluated are consistent with our (previously reported) empyrical observation that adjuvant surgery interspersed with courses of aggressive chemotherapy may render free of disease the majority of patients, prolong survival, and possibly cure a portion of this population.
Adenocarcinoma↗
[Toxicity of high-dose bleomycin administered by continuous infusion].
Fifteen patients with nonseminomatous testicular cancer underwent multidrug treatment which included cis platinum, Velban and bleomycin. The latter drug was administered in monthly 5 day courses of 100 mg/m2. No impairment of antitumor effect resulted since 12 of 15 patients had remissions (10 complete and 2 partial). Pulmonary toxicity was practically abolished: a median dose of 675 mg per patient (range 450 to 1050) was followed by normal lung X-ray and normal or near normal functional parameters after completing treatment. Median arterial oxygen pressure was 78 mm Hg (range 62 to 89), and median Tiffeneau index was 84 (range 64 to 87). Only 2 of 15 patients had skin marks from bleomycin toxicity at the end of treatment, so that cutaneous toxicity was also very low. Oral mucosa reversible damage was prominent in 2 patients. On the contrary, alopecia was a common finding.
Adolescent↗