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S Oriana

Publications and source records attributed to S Oriana.

At least 19 recordsLinked to original sources
PubMed2003

Vascular endothelial growth factor in node-positive breast cancer patients treated with adjuvant tamoxifen.

In 212 postmenopausal women with node-positive oestrogen receptor-positive (ER(LBA)) breast cancer subjected to radical surgery and adjuvant tamoxifen, the risk of 6-year relapse increased with increasing values of intratumoral vascular endothelial growth factor (VEGF) in patients whose tumours had a low/intermediate ER(LBA) content compared to patients with high-ER(LBA) tumours. These findings indicate that tumour progression, activated or sustained by high VEGF levels, may be counteracted in high-ER(LBA) cancers by tamoxifen, which in contrast fails to contrast the metastatic potential in low-ER(LBA) tumours.

Aged↗
PubMed2000

Time-dependent relevance of steroid receptors in breast cancer.

PURPOSE: To analyze the time-dependent prognostic role of the investigated variables, considered, when appropriate, on a continuous scale, for the purpose of evaluating and describing the interrelationships between clinically relevant patient and tumor characteristics (age, size and histology, and estrogen receptor [ER] and progesterone receptor content) and the risk of new disease manifestation. PATIENTS AND METHODS: We applied a flexible statistical model to a case series of 1,793 patients with axillary lymph node-negative breast cancer with a minimal potential follow-up of 10 years. To avoid a potential confounding effect of adjuvant treatment, only patients given local-regional therapy until relapse were considered. RESULTS: ER content and tumor size (adjusted for all the other covariates) showed a time-dependent relationship with the risk of new disease manifestations. In particular, ER content failed to show a prognostic effect within the first years of follow-up; thereafter, a positive association with risk of relapse was observed. For tumor size, within the first years of follow-up, the risk of relapse was directly related to size for only tumors up to 2.5 cm in diameter; thereafter, the impact on prognosis progressively decreased. CONCLUSION: The availability of a long follow-up on a large breast cancer series, as well as the use of innovative statistical approaches, allowed us to explore the functional relation between steroid receptors and clinical outcome and to generate a hypothesis on the involvement of ER in favoring long-term metastasis development.

Adult↗
PubMed1999

Combined sequential approach in locally advanced breast cancer.

BACKGROUND: The interaction between primary and adjuvant chemotherapy is a crucial point in the treatment of locally advanced breast cancer. OBJECTIVE: To evaluate the therapeutic efficacy of a sequential treatment with primary anthracyclines and adjuvant CMF in this patient subset. DESIGN: Prospective cohort study. PATIENTS: Eighty-eight breast cancer patients, stage T3b-T4 abc, N0-2, M0. RESULTS: From February 1991 to July 1994, 88 consecutive patients with locally advanced breast cancer were treated at the Istituto Nazionale Tumori, Milano, with full-dose doxorubicin (75 mg/m2) or epirubicin (120 mg/m2) for three cycles followed by surgery, adjuvant chemotherapy with i.v. CMF for six cycles and local radiotherapy +/- Tamoxifen. A high rate of objective responses (70%), but a low incidence of pathologic complete remission (2%), were observed following primary treatment with single-agent anthracyclines. Frequency of responses was not associated with tumor estrogen or progesterone receptors status, Mib-1 or grading. In 28 patients (32%) conservative surgery could be performed. At a median follow-up of 52 months, relapse free survival and overall survival are 52% and 62%, respectively. A multivariate analysis demonstrated a significant favorable prognosis in patients with limited nodal involvement at surgery and negative Mib-1 values. This drug sequence failed to significantly ameliorate the long term results in this unfavorable patient subset and more effective drug regimens and innovative therapeutic strategies are needed.

Adult↗
PubMed1999

Dose intensification of platinum compounds with glutathione protection as induction chemotherapy for advanced ovarian carcinoma.

Based on previous clinical experience indicating the tolerability and efficacy of high-dose cisplatin with glutathione protection in the treatment of advanced ovarian cancer, this study was undertaken to explore the efficacy and feasibility of an alternative high-dose, platinum-based approach including a combination of high-dose cisplatin plus carboplatin as induction chemotherapy of advanced ovarian carcinoma and intervention surgery. Fifty consecutive eligible patients with untreated stage III or IV epithelial ovarian cancer received 40 mg/m(2) cisplatin daily on days 1-4 and 160 mg/m(2) carboplatin on day 5. The cycle was repeated after 28 days. Patients received glutathione (2,500 mg) before each cisplatin or carboplatin administration and standard intravenous hydration. After 2 courses of induction chemotherapy, the patients underwent surgical reevaluation with debulking, when possible, followed by a further 3 cycles of 120 mg/m(2) cisplatin (i.e. 40 mg/m(2) daily for 3 consecutive days plus 600 mg/m(2) cyclophosphamide on day 3) except in instances of lack of response. All eligible patients were assessed for response and toxicity. The toxicity was moderate with lack of significant nephrotoxicity. Neurotoxicity and ototoxicity were acceptable and in no patient was treatment discontinued for those toxic effects. Myelotoxicity was somewhat more severe than that observed with our previous study with high-dose cisplatin and probably related to the addition of carboplatin. Of the 40 responsive patients, 23 (46%) had a pathological complete response and 4 (8%) had a clinical complete response (without second-look laparotomy). The efficacy of the present protocol was also documented by overall survival (median survival >48 months), which appeared to be better than expected with the current therapy in this group with advanced/bulky disease. The impressive efficacy suggests a possible contribution of reduced glutathione itself in improving the outcome, as supported by preclinical studies. The results of this study should be placed in context with current platinum-based therapy including paclitaxel.

Adult↗
PubMed1998

Is steroid receptor profile in contralateral breast cancer a marker of independence of the corresponding primary tumour?

We compared oestrogen receptor (ER) and progesterone receptor (PgR) profiles between primary and corresponding contralateral breast cancer (CBC) to investigate whether CBC should be considered relapse of a primary or as a feature of the multicentric origin of breast cancer. We adjusted for patient age, menopausal status, histology and adjuvant therapy. In spite of the general application of a cut-off value to dichotomise ER and PgR, we considered them as continuous variables. Moreover, we considered as synchronous cancers only simultaneously occurring lesions. For 399 patients, ER and PgR receptor levels in primary and CBC did not differ significantly, but were significantly correlated within the same patient. The correlation was higher for synchronous than for metachronous lesions when considering ER, but not PgR. The correlation between ER and PgR levels in the same tumour (primary or CBC) appeared stronger than the correlation of either receptor type (ER or PgR) between primary and CBC. Age, histology and adjuvant treatment affected ER concentration, whereas age, menopausal status and histology affected PgR concentration. The analysis indicated that primary and CBC tend to be characterised by a similar steroid receptor profile. The finding may support the hypothesis of CBC as a second primary arising in a common predisposing milieu, rather than a primary-dependent contralateral lesion. In this light, the clinical management of patients with a bilateral breast cancer should be similar to that of a unilateral breast cancer.

Adult↗
PubMed1996

Gene expression of DNA topoisomerases I, II alpha and II beta and response to cisplatin-based chemotherapy in advanced ovarian carcinoma.

DNA topoisomerases, nuclear enzymes that regulate DNA topology, are recognized as the primary targets of effective anti-tumor drugs. These enzymes may also have a role in the repair of DNA damage induced by alkylating agents and platinum compounds; therefore, their expression may be a determinant of tumor response to chemotherapy. Our study was undertaken in an attempt to establish a correlation between the enzyme expression and response of ovarian cancer to cisplatin-based chemotherapy. The expression of topoisomerase I, II alpha and II beta genes was assessed by RNase protection assay in tumor specimens obtained from 37 untreated patients with advanced epithelial ovarian cancer at initial surgery and from 13 pre-treated patients at subsequent laparotomy. The expression levels were compared with those found in 5 specimens from benign ovarian tissue and 5 specimens from normal ovarian tissue. The expression levels in untreated patients were used to establish a correlation with response to high-dose cisplatin therapy. A significant intertumor variability of mRNA expression was noted for all the genes examined. However, a comparison of median values indicated a remarkable increase of expression in malignant tumors over benign or normal tissues only for topoisomerase II alpha. This change is not related to alterations or amplification of topoisomerase II alpha gene. Interestingly, a correlation was found between tumor response to chemotherapy and the expression level of the isoform alpha (but not of topoisomerase II beta and topoisomerase I). The observed correlation suggests a contribution of the enzyme in determining tumor sensitivity. Alternatively, increased expression levels of the alpha isoenzyme gene in responsive tumors might reflect higher fractions of proliferating tumor cells that may be more drug-sensitive than resting cells.

Adult↗
PubMed1996

A comparative study of p53 gene mutations, protein accumulation, and response to cisplatin-based chemotherapy in advanced ovarian carcinoma.

The p53 protein is a multifunctional transcriptional regulator involved in cellular response to DNA damage and has been implicated as a putative determinant of sensitivity of tumor cells to cytotoxic agents. Since the p53 gene becomes inactivated in over one-half of advanced ovarian carcinoma, in this study we have examined the relationships between p53 gene alterations, p53 immunoreactivity, and response to cisplatin-based chemotherapy in ovarian cancer patients. All patients had advanced (FIGO stage III or IV) ovarian carcinoma and, with one exception, were untreated at the time of collection of tumor specimens. After initial debulking surgery, patients received high-dose cisplatin therapy. Tumor samples were analyzed for p53 gene mutations and for p53 protein accumulation, and the findings were correlated with tumor responsiveness. Of the 33 tumors examined, p53 gene mutations were found in 20 cases, including 15 missense mutations, 2 deletions, 2 nonsense mutations, and a base substitution at splice site. Twenty tumors showed positive immunostaining for p53. Only missense mutations were associated with positive immunostaining. In addition, p53 overexpression was detected in five tumors in the absence of mutations. Most (12 of 14) of the missense mutations associated with p53 protein stabilization were found refractory to therapy, as well as tumors overexpressing wild-type p53 (4 of 5). A significant correlation has been found between p53 accumulation, type of mutation (i.e., missense mutations), and pathological response to cisplatin-based therapy. In conclusion, the present results are consistent with a role of p53 as a determinant of chemosensitivity of ovarian carcinoma.

Alleles↗
PubMed1995

An I.T.M.O. group study on second-line treatment in advanced epithelial ovarian cancer: an attempt to identify clinical and biological factors determining prognosis.

The aim of the present study was to determine the activity of a combined regimen of mitoxantrone (DHAD) and ifosfamide (IFO) and identify clinical and biological factors with prognostic importance for the second-line treatment of ovarian cancer. The following factors were investigated for their prognostic importance: age, disease sites, platinum responsiveness, histological grade, the presence of clinically/radiologically detectable versus not detectable disease, residual disease volume after first surgery, p53 protein, c-erbB-2 oncoprotein and laminin receptor. 72 patients entered the trial. DHAD and IFO therapy led to a 15% response rate among the 47 cases with clinically/radiologically detectable disease (1 complete and 6 partial responses), with a median response duration of 4 months. The response rate was significantly different according to platinum responsiveness (4% objective responses in platinum-resistant versus 27% in platinum-sensitive disease). The time to treatment failure (TTF) and overall survival (OS) were affected by the presence of clinically detectable disease at study entry (median TTF 4 months in the presence of clinically/radiologically detectable disease versus 9 months if the disease was not similarly detectable, P = 0.02; median OS 10 months versus 21 months, P = 0.01). Initially overexpressed in only a few tumours, the c-erbB-2 oncoprotein became overexpressed in 36% of platinum-resistant tumours; this modulation did not occur in platinum-sensitive tumours. Furthermore, laminin receptor was expressed in 77% of platinum-sensitive versus 39% of platinum-resistant patients. There were no differences in p53 protein expression according to drug responsiveness.

Adult↗
PubMed1994

An intensive treatment with mitoxantrone and ifosfamide in second-line therapy of epithelial ovarian cancer.

AIMS AND BACKGROUND: Both mitoxantrone (DHAD) and ifosfamide (IFO) have given promising results when administered as single agents in advanced ovarian cancer pretreated with platinum compounds. The aim of this I.T.M.O. group pilot trial was to evaluate, in a selected population of ovarian cancer patients, the efficacy and tolerability of the following intensive second-line regimen: DHAD, 12 mg/m2 i.v., day 1; IFO, 4,000 mg/m2 i.v., days 1 and 2; Mesna, 800 mg/m2 i.v. t.i.d., days 1 and 2. Filgrastim (5 micrograms/kg/day i.m.) was given from day 6 to day 19 to reduce the expected neutropenia. Cycles were repeated every 21 days. METHODS: Nineteen platinum-pretreated patients were enrolled and 14 were evaluated for tumor response; the disease of 5 patients was not measurable clinically or radiologically. RESULTS: Seven responses were observed (3 CRs), with a median response duration of 5 months. The median time to treatment failure and overall survival for all 19 patients was respectively 8 and 13 months. Anemia was observed in all of the treated patients (grade 3-4 in 9 cases). Only 6 of the 19 patients ended the five planned cycles of chemotherapy without any delay. CONCLUSIONS: Although DHAD plus IFO induced a considerable number of objective responses, the limited response duration time to treatment failure, and overall survival as well as the reported side effects suggest that this is not a recommended regimen for the palliative treatment of ovarian cancer patients undergoing second-line chemotherapy.

Adult↗
PubMed1994

Control of nausea and vomiting by granisetron in ovarian cancer patients treated with different cisplatin-based regimens.

AIMS: The study evaluated the safety and efficacy of granisetron as an antiemetic drug in ovarian cancer patients treated with cisplatin-based chemotherapy. STUDY DESIGN: Two groups of consecutive patients were considered: the first (Group A) with advanced disease, receiving 4-day cisplatin therapy in a 40 mg/m2 daily dose; the second (B), with minimal disease after radical surgery at high risk of recurrence, treated by single-day chemotherapy with a 90 mg/m2 dose. In both groups, 3.0 mg of granisetron was administered as a 10 min. intravenous infusion, 30 min. before cisplatin infusion. The treatment schedule included in all patients the administration of 125 mg i.v. of methylprednisolone 2 h before chemotherapeutic infusion. No further doses of granisetron were allowed within each 24 h study period for breakthrough nausea and vomiting. Assessment for nausea and vomiting was made at 24 h intervals through the 6-day study period for both groups using a diary card. RESULTS AND CONCLUSION: In group A, 25 patients were collected and evaluated; in group B, 25 were recruited and 13 evaluated. In both groups, excellent control of nausea and vomiting was achieved, since in group A we had a global major antiemetic efficacy of granisetron in 69.2% of patients (54.4% complete control and 14.8% major control); in group B, global major efficacy was present in 83.3% of cases (31.6% complete control and 51.7% major control). The antiemetic effect in the days following antiblastic treatment lasted longer in group A.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

The intramuscular administration of granulocyte colony-stimulating factor as an adjunct to chemotherapy in pretreated ovarian cancer patients: an Italian Trials in Medical Oncology (ITMO) Group pilot study.

No published data are available concerning the activity and tolerability of intramuscularly administered granulocyte colony-stimulating factor (G-CSF) in humans. To fill this gap, 19 patients with advanced ovarian cancer previously treated with at least one first-line chemotherapy cycle received the following myelosuppressive regimen: mitoxantrone (DHAD) 12 mg m-2 i.v. on day 1; ifosfamide (IFO) 4 g m-2 i.v. on days 1 and 2; mesna 800 mg m-2 i.v. t.i.d. on days 1 and 2. G-CSF (Filgrastim) was given at a dose of 5 micrograms/kg/day i.m. from day 6 to day 19, its pharmacokinetics being assessed in five patients. The neutrophil nadir was observed after a mean period of 8 days, and the neutrophil count was < 1.0 x 10(3) mm-3 for a mean of 6 days during the cycle of chemotherapy. The neutrophil count fell after the withdrawal of G-CSF on the 19th day of treatment. The difference in absolute neutrophil count between day 19 and day 21 was statistically significant (P = 0.0001); nevertheless, at day 21 no WHO grade 3-4 neutropenia was reported. DHAD and IFO were respectively given at 95% and 93% of the planned dose. The pharmacokinetics of G-CSF i.m. seems to be similar to that of the drug given subcutaneously. No evidence of cumulative myelosuppression was observed. G-CSF was well tolerated and no complications were observed at the injection sites. In conclusion, if the results obtained in this pilot study regarding the activity of i.m. G-CSF are confirmed by a randomised trial, the intramuscular administration of G-CSF could become a valid alternative for patients who dislike the subcutaneous route and who are being treated with chemotherapy that does not induce profound thrombocytopenia.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

In vitro cytotoxic activity of Taxol and Taxotere on primary cultures and established cell lines of human ovarian cancer.

The activity of Taxol and Taxotere was evaluated on three established cell lines and 19 primary cultures of human ovarian cancers and compared with that of cisplatin and doxorubicin. The cytotoxic activity of the different drugs was assessed with a clonogenic assay in cell lines and with a proliferative assay (based on [3H]thymidine [3H-dT] incorporation of cells grown in double-layer agarose for four days) in primary tumor cultures. The two assays run in parallel on the OVCA432 cell line provided similar ranking of activity for all the drugs. Taxotere was more cytotoxic than Taxol in two cell lines and showed the same degree of activity in one cell line. Moreover, the two drugs were more cytotoxic than cisplatin and doxorubicin in all cell lines. In primary cultures both Taxol and Taxotere were less active than cisplatin and doxorubicin. An activity by at least one of these two compounds was seen in 9 of 19 cases. Taxol was more frequently active than Taxotere and generally more potent. A direct relationship was observed between the proliferative activity of the tumor cell population and response to Taxol and/or Taxotere. In fact, cell lines that were highly sensitive to Taxol and Taxotere displayed 3H-dT labeling index (LI) values much higher than those observed in primary cultures (39% to 45% versus 0.2% to 12.6%). Again, primary cultures sensitive to Taxol and/or Taxotere were characterized by a median 3H-dT LI value about three times higher than that observed in resistant cultures (8.0% versus 2.6%).

Carcinoma↗
PubMed1993

Urinary testosterone as a marker of risk of recurrence in operable breast cancer.

We investigated the role of urinary testosterone levels as a marker of risk of recurrent disease in 113 operable breast cancer patients (70 premenopausal, 43 postmenopausal). Twenty-four-hour urine collections for testosterone measurement were obtained before surgical treatment, between 20-40 days thereafter, and then every 6 months for 5 years. The cutoff values to separate 'high testosterone (A+)' from 'normal testosterone (A-)' were 8.0 micrograms/24 h in premenopause and 4.9 micrograms/24 h in postmenopause. Urinary testosterone levels were considered high when they exceeded the cutoff value in at least 2 of the first 3 measurements (pretreatment, post-treatment, 6 months) of each patient. According to the aforementioned criterion, 33 patients (29.2%) had high testosterone levels, which were associated to axillary node involvement in 16 patients. Thirteen of the latter relapsed during the 5-year follow-up period (5/7 in premenopause, 8/9 in postmenopause). Relapse-free survival (RFS) curves were drawn only for node-positive patients owning to the small number of recurrences observed in the node-negative group. In premenopausal node-positive patients, RFS was significantly different for patients presenting high and normal urinary testosterone levels (77% vs 28%, respectively; logrank test, p < 0.006). In postmenopausal node-positive patients, RFS was also different between the two groups (54% vs 11% in 'high' and 'normal' excretors, respectively) but the difference was not statistically significant. The present findings suggest that urinary testosterone is a prognostic indicator of early breast cancer recurrence in node-positive patients.

Adult↗
PubMed1993

High-dose cisplatin and cyclophosphamide with glutathione in the treatment of advanced ovarian cancer.

BACKGROUND: On the basis of preliminary results achieved with a high-dose cisplatin regimen including glutathione as chemoprotector, the efficacy and toxicity of the new regimen was further evaluated in a larger series of patients with advanced ovarian cancer (stage III and IV). PATIENTS AND METHODS: The study included patients with bulky or extensive residual disease after primary laparotomy or with bulky inoperable tumor masses. A total of 79 patients were treated with up to five courses of high-dose cisplatin (40 mg/m2 daily in normal saline, for four days) plus glutathione (2500 mg as a short-term infusion before cisplatin), together with cyclophosphamide (600 mg/m2 as an i.v. bolus on day 4). A standard i.v. hydration consisting of a total of 2000 ml of fluids without diuretics was employed. RESULTS: All eligible patients, who received a total of 345 courses, were assessed for response and toxicity and 52 received the planned five courses of the protocol. Forty-five patients (57%) achieved complete clinical responses and 20 (25%) had partial remissions for an overall response rate of 82%. The response rate was critically dependent on tumor size before chemotherapy. Thirty-eight of 45 patients who had complete clinical responses underwent second-look laparotomy, and 29 had pathological complete responses (37%). Seventeen of these 29 patients subsequently relapsed (median disease-free interval, 12 months; range, 6-45). With a median follow-up time of 44 months, the median survival for the 79 analyzed cases was 40 months. The toxicity of the regimen was moderate. Nausea/vomiting was the most severe acute toxicity. Myelotoxicity was acceptable, with severe leukopenia and thrombocytopenia (grade 4) occurring in 8% and 3% of patients, respectively. Nephrotoxicity was minimal with a transient increase (to < 2 mg/dL) in serum creatinine in only 6 patients (8%). Peripheral neurotoxicity and ototoxicity were the most significant long-term toxicities. The severity of these side effects (grade 3 WHO neurotoxicity occurred in only 4% of patients) was apparently less than has been reported with other high-dose cisplatin regimens. Neurotoxicity required discontinuation of therapy in three patients after four courses. Most affected patients had complete or partial recovery of symptoms with time. DISCUSSION: The efficacy and tolerability of the regimen confirm the feasibility of this new approach including glutathione in order to increase cisplatin dose intensity. The superiority of this regimen over standard induction therapy should be confirmed in randomized trials.

Adult↗
PubMed1992

Peripheral neurotoxicity following high-dose cisplatin with glutathione: clinical and neurophysiological assessment.

The use of high-dose cisplatin is limited by development of severe peripheral neurotoxicity and gradual worsening of renal function. In an ongoing study of high-dose cisplatin glutathione has been employed with the aim of preventing major cisplatin-induced toxicities. Neurotoxicity was examined in detail in 32 patients with ovarian cancer treated with cisplatin (160 mg/m2) and cyclophosphamide (600 mg/m2) every 3-4 weeks for five courses. In addition to serial complete neurological examination, sensory action potentials (SAPs) and motor conduction velocities (MCVs) were also assessed. We confirmed the development of a predominant sensory involvement, characterized by mild distal paresthesias and decrease in vibratory sensibility and in deep tendon reflexes, with a slight reduction of SAPs, observed after three courses of treatment. After five courses, distal paresthesias and disesthesias, decreased proprioception and loss of vibratory sensibility with ataxic signs, absence of deep tendon reflexes, unobtainable SAPs and only moderately reduced MCVs were seen. We did not observe any case of disabling neuropathy. There was a tendency to a more severe involvement of peripheral nerves in patients aged more than fifty. The 3 patients presenting the most serious neuropathy were the oldest in the whole group. Low degree of neurotoxicity observed in this study supports a glutathione protection against cisplatin-induced neurotoxicity. As the urinary excretion of platinum indicated no changes in the renal clearance of cisplatin following repeated courses, the lack of drug accumulation and high plasma peak due to preserved renal function might explain the reduced neurotoxicity observed.

Adult↗
PubMed1990

Efficacy and safety of high-dose cisplatin and cyclophosphamide with glutathione protection in the treatment of bulky advanced epithelial ovarian cancer.

Recent efforts to improve the response rates in advanced ovarian cancer with the use of high-dose cisplatin have been limited by unacceptable toxicity. Based on experimental and clinical studies indicating that reduced glutathione (GSH) is a protective agent against cisplatin-induced toxicity, a new high-dose regimen including GSH as a chemoprotector was designed in an attempt to improve the efficacy and therapeutic index of cisplatin. A total of 40 consecutive patients with stage III (bulky) and IV ovarian carcinoma were treated with cisplatin (40 mg/m2 daily for 4 consecutive days) and cyclophosphamide (600 mg/m2 i.v. on day 4). The treatment was repeated every 3-4 weeks for five courses unless progression or severe toxicity occurred. Before each cisplatin administration, patients received GSH (1,500 mg/m2) i.v. over 15 min, with a standard i.v. hydration (2,000 ml fluid) without diuretics. Debulking surgery was initially attempted in 18 patients and, after 2-3 courses, in 16 patients; it could not be carried out in 6 patients. Three patients were not evaluable for response because they prematurely discontinued their treatment. In all, 23 patients (62%) achieved complete clinical remission (negative second-look laparotomy in 16), with an overall (complete + partial) response rate of 86%; 2 patients achieved disease-free status following second surgery. Nausea/vomiting was the most severe acute toxic effect; myelosuppression was acceptable. Renal impairment was effectively prevented by GSH. Neurotoxicity that was not associated with motor dysfunction was the most significant cumulative toxicity in patients (24/32) receiving 4-5 courses. The results of this study indicate that the use of GSH is a safe new method for high-dose cisplatin administration. This regimen is well-tolerated and very effective in ovarian cancer patients with bulky disease and warrants further evaluation.

Adult↗