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Biomedical subjects

E Cvitkovic

Publications and source records attributed to E Cvitkovic.

At least 37 records · Page 2Linked to original sources
PubMed2001

[Oxaliplatin: a first DACH-platinum in oncology].

Around 3,000 cisplatin analogues have been synthetised over the past 30 years but only half a dozen are presently in clinical development, while only two (cisplatin and carboplatin) have been available prior to the recent European registration of oxaliplatin. Oxaliplatin is a new platinum salt belonging to the DACH (diaminocyclohexane) platinum family, and is the only such cisplatin analogue that has entered clinical development and achieved approval for marketing. During its development, oxaliplatin has aroused lively interest due, firstly, to its in vitro and in vivo antitumoral activity, especially in cisplatin-resistant models and cell lines expressing resistance genes, and, secondly, to its good clinical tolerance, the absence of renal or auditory toxicity being combined with a low hematotoxicity. Combined with other antitumoral agent cytotoxic agents (5FU, raltitrexed, irinotecan or cisplatin), oxaliplatin produces an additive and often synergistic cytotoxic effect. The oxaliplatin-5FU +/- FA combination is now well established in metastatic colorectal cancer. Regarding its particular cytotoxic characteristics and its activity in mismatch repair deficient cells (which are resistant to cisplatin and carboplatin), oxaliplatin is shows potential in a large variety of solid tumor types, notably in association with other cytotoxic agents, thus opening the path to a wider range of indications.

Antineoplastic Agents↗
PubMed2000

Combination raltitrexed (Tomudex(R))-oxaliplatin: a step forward in the struggle against mesothelioma? The Institut Gustave Roussy experience with chemotherapy and chemo-immunotherapy in mesothelioma.

The aim of this study was to review the experience of the Institut Gustave Roussy in 163 patients with malignant mesothelioma over a 9-year period. Data from seven consecutive prospective trials, four of chemo-immunotherapy and three of chemotherapy were reviewed. The rationale, methods and results of these trials are summarised and discussed. 98 patients were included in four phase II trials of chemo-immunotherapy whose common denominator was a combination of cisplatin and alpha-interferon. The response rate ranged from 15% to 40%. High-dose weekly cisplatin combined with alpha-interferon yielded the highest response rate but the toxicity of this regimen was considered unacceptable. Neither higher doses of alpha-interferon or the addition of mitomycin C or interleukin-2 to the regimen were able to enhance the activity of this combination. 18 patients were included in a paclitaxel-cisplatin phase II trial. The response rate was only 6% (95% confidence interval (CI): 0-24) and toxicity was also significant. This regimen was, therefore, considered ineffective. Of 17 patients with mesothelioma included in a phase I trial that combined raltitrexed and oxaliplatin, 6 (35%) obtained a partial response. Responses were seen even in cisplatin-refractory mesothelioma. Preliminary results of a subsequent ongoing phase II trial using raltitrexed (3 mg/m(2)) and oxaliplatin (130 mg/m(2)) have confirmed this promising activity with a 30% (9/30) response rate (95% CI: 15-49). The tolerance of this outpatient regimen is acceptable (no significant haematological toxicity and no alopecia) and compares favourably with that of our previous regimens. The final results concerning response and survival are required to confirm the efficacy of this combination. The preliminary results of two studies suggest promising activity with the combination of raltitrexed-oxaliplatin in malignant mesothelioma. The efficacy/toxicity ratio of this combination compares favourably with that of our previous chemotherapy and chemo-immunotherapy regimens.

Adult↗
PubMed2000

Factors predicting for efficacy of oxaliplatin in combination with 5-fluorouracil (5-FU)+/-folinic acid (FA) in a compassionate-use cohort of 370 5-FU-resistant advanced colorectal cancer (CRC) patients.

Univariate and multivariate analyses were performed on data from 370 5-fluorouracil (5-FU)-resistant advanced colorectal cancer patients treated with oxaliplatin (Eloxatin)/5-FU+/-folinic acid (FA) to identify prognostic factors for oxaliplatin-based treatment. The response rate was 14.6% (95% confidence interval (CI): 11.0-18.2%), median time to progression was 4.3 months (95% CI: 3.9-4.7), and median overall survival 9.7 months (95% CI: 8.5-10.8). Multivariate analysis indicated < 2 prior chemotherapy regimens, bi-weekly treatment administration schedule (versus tri-weekly) and continuous chronomodulated delivery (CCM) as significantly associated (P < 0.05) with a higher overall response rate. Performance status (PS) < 2, having only one involved organ, biweekly schedule and CCM were associated (P < 0.05) with a longer time to progression. Good PS, one involved organ, low alkaline phosphatase (AP) serum levels, bi-weekly schedule and CCM were significantly correlated with longer overall survival, while confirming the efficacy of oxaliplatin/5-FU+/-FA in this indication.

Adult↗
PubMed2000

Oxaliplatin clinical activity: a review.

Oxaliplatin (Eloxatin), a recently developed third-generation cisplatin analogue with a 1,2-diaminocyclohexane (DACH) carrier ligand, has displayed preclinical and clinical activity in a wide variety of tumour types. Synergistic with 5-FU in colorectal cancer (CRC), the combination has proven efficacy in 5-FU-resistant advanced disease and in previously untreated CRC, as demonstrated in controlled phase III trials, while evaluation in the adjuvant setting is ongoing. Due to its excellent safety profile, its unique mechanism of action and lack of cross-resistance with other active agents in CRC, oxaliplatin has also been combined with CPT-11 and Raltitrexed with promising results. Trials in pretreated and untreated advanced ovarian cancer (AOC), as a single agent or in combination with cisplatin, cyclophosphamide or paclitaxel, indicate a yet to be defined role in AOC and confirm its lack of cross-resistance with cis/carboplatin. Clinical investigations of single agent and combination therapies in breast, lung, prostate and germ-cell carcinomas, non-Hodgkin's lymphoma and malignant mesothelioma are being pursued. While the role of oxaliplatin in medical oncology is yet to be fully defined, it appears to be an important new anticancer agent.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Dose escalation of CPT-11 in combination with oxaliplatin using an every two weeks schedule: a phase I study in advanced gastrointestinal cancer patients.

BACKGROUND: To determine the dose-limiting toxicity of CPT-11 in combination with oxaliplatin, and the maximal tolerated dose (MTD) and the recommended dose (RD) of CPT-11 using an every two weeks schedule. PATIENTS AND METHODS: The study was designed to evaluate escalated doses of CPT-11 starting at 100 mg/m2 with a fixed clinically-relevant dose of 85 mg/m2 oxaliplatin given every two weeks. RESULTS: Twenty-three patients and 186 cycles were evaluable for toxicity (median per patient: 7, range: 1-13). Grade 3 oxaliplatin-induced neurotoxicity was cumulative and limiting in 39% (9 of 23) of patients. The MTD of CPT-11 was 200 mg/m2, with incomplete neutrophil recovery at day 15 as limiting toxicity. At the RD (175 mg/m2 of CPT-11): no grade 4 neutropenia was seen in the two first cycles; 30% of patients experienced grade 3-4 diarrhea. Febrile neutropenia (3.2% of all cycles) was 3-fold more frequent in performance status (PS) 2 than in PS0-1 patients. Among eleven colorectal cancer (CRC) patients, three complete and four partial responses were documented, including in three 5-fluorouracil (5-FU) refractory patients. CONCLUSION: To combine CPT-11 175 mg/m2 and oxaliplatin 85 mg/m2 every two weeks is feasible in an outpatient setting, and very active in 5-FU resistant CRC patients. A dose of 150 mg/m2 CPT-11 is recommended in PS2 patients.

Adult↗
PubMed2000

Pilot study of the paclitaxel, oxaliplatin, and cisplatin combination in patients with advanced/recurrent ovarian cancer.

To determine the feasibility of the paclitaxel, oxaliplatin, cisplatin combination in advanced ovarian cancer (AOC), 15 patients with AOC (8 chemonaive, and 7 second-line, disease-free interval > or = 12 months) received paclitaxel 135 mg/m2 at day 1, with oxaliplatin 100 mg/m2 and cisplatin 75 mg/m2 at day 2, every 3 weeks for 6 cycles. Pretreated patients received prophylactic granulocyte colony-stimulating factor (5 microg/kg/d, days 6-13). Seventy cycles were administered; median 5 (range: 2-6 cycles) in chemonaive, and 4 (range: 2-6) in pretreated patients. There were grades III to IV neutropenia in 77%, febrile neutropenia in 24%, and grades III to IV thrombocytopenia in 4% of the cycles. Besides neutropenia, cumulative neurosensory toxicity was also limiting although reversible, with National Cancer Institute Common Toxicity Criteria grades II to III observed in 13 patients. Three of the pretreated patients had complete responses (43%), three had partial responses, and one had disease stabilization. Six of the 8 chemonaive patients had complete responses (75%), 1 had disease stabilization, and 1 had disease progression. The median follow-up is 17 months (range: 9-20 months) in chemonaive and 41 months (range: 13-58 months) in pretreated patients, and time to progression has been consistently more than 12 months, with 6 patients (5 chemonaive) still progression free (range: 15+ to 22+ months). This active combination shows acceptable hematologic toxicity, and reversible cumulative neurosensory toxicity. Further clinical exploration of the present combination appears warranted.

Adult↗
PubMed2000

Factors predicting for efficacy and safety of docetaxel in a compassionate-use cohort of 825 heavily pretreated advanced breast cancer patients.

PURPOSE: To identify predictive factors for efficacy and safety in advanced breast cancer (ABC) patients treated in the French compassionate-use docetaxel program. PATIENTS AND METHODS: A total of 825 ABC patients treated with docetaxel (100 mg/m(2) every 3 weeks) were source-reviewed and analyzed for prognostic factors associated with overall response rate (ORR), time to treatment failure (TTF), overall survival (OS), febrile neutropenia, mucositis, and severe fluid retention syndrome by univariate and multivariate analysis. RESULTS: The ORR was 22.9% (95% confidence interval, 20.2% to 26.2%). The median TTF and OS were 4.0 and 9.8 months, respectively. By multivariate analysis, secondary anthracycline-resistant disease was significantly associated (P <. 05) with lower ORR and shorter TTF and OS, whereas anthracycline-refractory disease was associated with shorter OS. Poor performance status was associated with lower ORR, shorter TTF, and shorter OS. Liver dysfunction (transaminase levels > 1.5 times the upper limit of normal [ULN] and alkaline phosphatase [AP] level > three times ULN) and time since first relapse less than 24 months were associated with shorter TTF and OS. Other significant correlations included the following: elevated CA 15-3 serum level with lower ORR; more than two involved sites, and minor transaminase and AP level abnormalities with shorter OS; and no previous chemotherapy for ABC with shorter TTF. According to multivariate analysis, ORR, TTF, and OS were not decreased in patients with liver metastases but without liver dysfunction. CONCLUSION: Docetaxel activity was maintained in heavily pretreated ABC patients and in those with liver metastasis; docetaxel must be used cautiously, however, in patients with liver dysfunction in whom high morbidity risk necessitates strict adherence to dose-adaptation guidelines.

Anthracyclines↗
PubMed2000

Long-term disease-free survivors in metastatic undifferentiated carcinoma of nasopharyngeal type.

PURPOSE: To review incidence and analyze profile of long-term complete responders among patients with undifferentiated carcinoma of nasopharyngeal type (UCNT) treated at a single institution. PATIENTS AND METHODS: We present a cohort of 20 long-term unmaintained complete responders to chemotherapy for metastatic UCNT treated at the Institut Gustave Roussy between April 1978 and November 1996. A patient was considered a long-term survivor if he or she was disease-free for more than 36 months without treatment after obtaining a complete response by chemotherapy. Patient characteristics were as follows: sex, 17 men and three women; median age, 28 years (range, 9 to 62 years); median World Health Organization performance status, 1; and initial tumor-node-metastasis stage (International Union Against Cancer-American Joint Committee on Cancer, 1987) of T3 to T4, 60%, and of N2b to N3, 75%. Epstein-Barr virus serology was characteristic in 19 patients. Of 16 pretreated patients, 11 were pretreated by radiotherapy alone and five by chemotherapy and radiotherapy. Thirteen patients had metastatic relapses of locally controlled UCNT. Tumor sites were bone in 15 patients, lung in four, and liver (biopsy-proven) in two. Chemotherapy included the following: cisplatin, bleomycin, and fluorouracil in five patients; bleomycin, epirubicin, and cisplatin in seven patients; fluorouracil, mitomycin, epirubicin, and cisplatin in four patients; and fluorouracil, bleomycin, epirubicin, and cisplatin in one patient. Three patients were treated with platinum-based regimens before 1985. Patients received a median of six cycles (range, three to 13). Thirteen patients with bone metastases received consolidating radiotherapy. RESULTS: As of June 1999, 14 of 20 patients were still alive with no evidence of disease after treatment (disease-free survival time, 82+ to 190+ months), three patients died of other causes while in complete response at 61, 109, and 208 months after treatment, and three patients died of disease at 42, 89, and 115 months after treatment. Long-term complete responses were obtained in both bone and visceral disease. CONCLUSION: Our data support a curative role for chemotherapy in metastatic UCNT and are a major incentive to continue research for better combinations to increase the percentage of patients with metastatic UCNT who attain complete responses and long-term survival.

Adolescent↗
PubMed2000

[Epidermoid carcinoma of the head and neck: contribution of chemotherapy in case of recurrence and locally advanced disease. Review of the literature].

Epidermoid carcinoma of the head and neck accounts for 10% of all cancers. At diagnosis, 60% of patients have a locally advanced disease, leading to high mortality and major functional handicaps. Chemotherapy has been shown to be active in patients presenting metastatic and/or locoregional recurrence, with 20 to 30% response rates, although no clearly established survival benefit has been demonstrated. Combining chemotherapy with surgery and/or radiotherapy has become possible with the development of new drugs and has recently led to major changes in management protocols for locally advanced epidermoid carcinoma of the head and neck. Therapeutic gain has been focalized on improving locoregional control, decreasing metastatic spread, and on the concept of an organ conservation strategy with schedules including chemotherapy as an inducing, concomitant, or alternating treatment with radiotherapy. Although many agents have demonstrated their efficacy, the role of chemotherapy in epidermoid carcinoma of the head and neck is not totally defined. The aim of treatment in metastatic and/or locoregional recurrent disease is palliative care. Regimens associating cisplatinum give a high response rate in patients previously untreated, without any real benefit in terms of survival. An evaluation of the activity of new agents with novel modes of action is currently under way. In locally advanced disease, concomitant chemotherapy with radiotherapy seems to give a minimal but real benefit as evidenced in the different meta-analyses recently published.

Carcinoma, Squamous Cell↗
PubMed2000

Pharmacokinetics and pharmacodynamics of the novel marine-derived anticancer agent ecteinascidin 743 in a phase I dose-finding study.

Ecteinascidin (ET) 743 is an anticancer agent derived from the Caribbean tunicate Ecteinascidia turbinata. Preclinical studies revealed activity of ET-743 against different tumor types. A Phase I clinical trial was designed with ET-743 to identify the maximum tolerated dose and dose-limiting toxicities (DLTs). Furthermore, the pharmacokinetics of ET-743 and relationships with pharmacodynamics were evaluated. Adult patients with solid, resistant tumors received ET-743 as a 24-h i.v. infusion every 21 days. Blood samples were obtained during the first treatment course and in several consecutive courses. Noncompartmental pharmacokinetic analysis was performed. Relationships between pharmacokinetics and hepatic and hematological toxicities were explored. Fifty-two patients were treated at nine dose levels (50-1800 microg/m2). The DLTs, neutropenia and thrombocytopenia, were experienced at 1800 microg/m2. Twenty-five patients were treated at the recommended Phase II dose of 1500 microg/m2. At this dose, the mean value +/- SD for total body clearance was 59 +/- 31 liters/h, and the mean t(1/2) was 89 +/- 41 h. Pharmacokinetics were linear over the dose range tested. Prior exposure to ET-743 did not alter the pharmacokinetics in subsequent courses. The percentage of decrease in WBC count and absolute neutrophil count was correlated to the area under the plasma concentration versus time curve (AUC). Hepatic toxicity, defined as rise in alanine aminotransferase and aspartate aminotransferase, increased with dose and AUC but was reversible and not dose limiting. In conclusion, ET-743 administered as a 24-h i.v. infusion at a dose of 1500 microg/m2 is clinically feasible; severe thrombocytopenia and neutropenia are the DLTs.

Adult↗
PubMed1999

Phase II trial of chemotherapy with 5-fluorouracil, bleomycin, epirubicin, and cisplatin for patients with locally advanced, metastatic, or recurrent undifferentiated carcinoma of the nasopharyngeal type.

BACKGROUND: The aim of this study was to evaluate the toxicity and efficacy of the combination of 5-fluorouracil, bleomycin, epirubicin, and cisplatin (FBEC) in the treatment of patients with undifferentiated carcinoma of nasopharyngeal type (UCNT). The study included patients with metastatic or recurrent disease (Group A) and previously untreated patients with locally advanced nonmetastatic disease (T >/= 3 or any T, N >/= 2, M0, according to 1987 criteria of the International Union Against Cancer and the American Joint Committee on Cancer (Group B). METHODS: From January 1992 to November 1996, 49 patients with histologically proven UCNT were treated with intravenous (i.v.) 5-fluorouracil (700 mg/m(2)/day by continuous infusion for 4 days), epirubicin (70 mg/m(2) i.v. on Day 1), Bleomycin (10 mg i.v. bolus on Day 1 followed by 12 mg/m(2)/day by continuous infusion for 4 days), and cisplatin (100 mg/m(2) on Day 5); this regimen was repeated every 21 days. Six cycles were given to Group A (26 patients), with bleomycin omitted during the last 3 cycles. In Group B (23 patients), only 3 cycles were given, followed by conventional radiotherapy (70 gray for 7 weeks). RESULTS: Of the 26 patients entered in Group A, 23 were evaluable for response. Nine complete responses (CRs) and 9 partial responses (PRs) were assessed, for a 78% objective response rate (ORR) (95% CI: 56-92). Three patients are alive with no evidence of disease after 43, 61, and 73 months, respectively. These patients achieved a CR with chemotherapy followed by consolidating radiotherapy to their target lesions. In Group B, the ORR was 91.5%, with 5 CRs (22%) and 16 PRs (69.5%) assessed in the 23 patients. Three months after the end of radiotherapy, the ORR was 87% (20 patients). After a median follow-up of 51 months (range, 24-67 months), 15 patients (65%) are alive without evidence of disease. Forty percent of cycles (51% in Group A, 25% in Group B) resulted in Grade 4 neutropenia, with fever and/or sepsis in 9.5%. Mucositis was seen in 42% of pretreated patients. There were 3 treatment-related deaths (2 from complications of infection and 1 bleomycin fibrosis at a total dose of 160 mg/m(2)), all of them in Group A. CONCLUSIONS: The FBEC regimen has good activity, with durable responses in patients with locally advanced, metastatic, or recurrent UCNT. This regimen is safe for patients with locally advanced disease, but close follow-up and supportive measures are needed when it is used to treat those with metastatic or recurrent disease.

Adolescent↗
PubMed1999

Supraadditive effect of 2',2'-difluorodeoxycytidine (gemcitabine) in combination with oxaliplatin in human cancer cell lines.

PURPOSE: This study assessed the cytotoxic effects of the nucleoside analog gemcitabine in combination with the diaminocyclohexane platinum compound oxaliplatin. METHODS: Growth inhibition studies were performed using the human CEM leukemia cell line and the colon-cancer cell lines HCT 116 and Colo 320 DM. Gemcitabine-oxaliplatin combinations were compared with gemcitabine-cisplatin combinations in the same cell lines using similar experimental settings. Cells were exposed for 2 h to gemcitabine and then for 24 h to oxaliplatin or cisplatin, and vice versa. RESULTS: The 50% inhibitory concentrations (IC50 values) in single-drug experiments using 2 h of exposure to gemcitabine and 24 h of exposure to oxaliplatin or cisplatin were, respectively, 89 pM, 11.1 microM, and 10.3 microM for CEM cells; 46 pM, 10.2 microM, and 2.7 microM for HCT 116 cells; and 102 pM, 4.6 microM, and 8.6 microM for Colo 320 DM cells. Gemcitabine-oxaliplatin combinations displayed supraadditive effects in human leukemia and colon-cancer cell lines. The sequence of gemcitabine followed by oxaliplatin was more effective than the opposite sequence in HCT 116 and Colo 320 DM colon-cancer cell lines, whereas the sequence of oxaliplatin followed by gemcitabine yielded to synergistic effects in CEM cells. The cytotoxic effects of gemcitabine-oxaliplatin combinations were better than (HCT 116 cells) or equal to (CEM and Colo 320 DM cells) those of gemcitabine-cisplatin combinations. CONCLUSION: Our data show that the combination of gemcitabine with oxaliplatin exerts potent antiproliferative effects in human leukemia and colon cancer cells, warranting further investigations in the framework of phase I-II trials as an alternative for the treatment of solid malignancies.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Antitumoral activity of oxaliplatin/cisplatin-based combination therapy in cisplatin-refractory germ cell cancer patients.

PURPOSE: Only 20-30% of patient with advanced germ cell tumors, relapsing after standard first-line therapy, are curable with current second-line cisplatin-based regimens. New salvage combinations incorporating new active agents are needed. We report the toxicity/tolerance of a new salvage regimen based on the oxaliplatin (Eloxatin)/cisplatin combination, evaluated in patients with recurrent, mostly cisplatin-refractory germ cell tumors. PATIENTS AND METHODS: Thirteen patients were enrolled in this study. All except one had received cisplatin-based chemotherapy. Eight had progressive disease as the best response on their last platinum-based chemotherapy, and three had potentially sensitive tumors. The median interval since the last platinum-based chemotherapy was 6 months (range: 1-36 months). One untreated patient with poor prognosis was also enrolled. Twelve patients had pathological markers [median alpha-fetoprotein 14 800 ng/ml (58-10(6)), median human chorionic gonadotrophin beta subunit 7000 IU/ml (37-723 700)]. Patients received either oxaliplatin (130 mg/m(2)) and cisplatin (100 mg/m(2)) every 3-4 weeks (Bi regimen, four patients), or the same regimen combined with one to four of the following cytotoxic agents: ifosfamide, epirubicin, vinorelbine, methotrexate, dactinomycin, etoposide and bleomycin (BiC regimen, 9 patients). Treatment was individualized according to each individual patient's pretreatment and clinical characteristics. RESULTS: Seven objective responses were obtained (overall response rate = 54%), all with the BiC regimens (two complete and five partial responses). Two patients with recurrent disease achieved a long-term complete response lasting over 5 years. Four partial responders were seen in the eight cisplatin-refractory tumors, lasting 4-8 months. All objective responses had a corroborating major decrease in tumor marker blood levels (median decrease: 99.7%). The median survival for the whole group was 8 months. The commonest severe toxicity was hematological (grade 4 neutropenia in 78% and thrombopenia in 74% of the BiC cycles). CONCLUSION: Our combined salvage regimen induced significant antitumoral activity in recurrent, cisplatin-refractory germ cell tumors. Oxaliplatin merits further evaluation as a component of combination therapy for this disease.

Adolescent↗
PubMed1999

Differential regulation of normal and tumoral breast epithelial cell growth by fibroblasts and 1,25-dihydroxyvitamin D3.

Mesenchymal-epithelial interactions are of paramount importance during normal and tumoral breast developments. We have investigated the paracrine growth regulation of normal and tumoral breast epithelial cells by fibroblasts derived from normal or pathological breast tissues. In some cases, breast cancer MCF-7 cells or normal epithelial cells in primary culture were cocultured with fibroblasts in a Transwell system allowing diffusible factor exchanges. Alternatively, conditioned medium produced by fibroblast cultures was added to epithelial cell cultures. Fibroblasts were shown to stimulate the proliferation of normal and carcinoma cells through paracrine mechanisms. However, the paracrine exchanges appeared to be different in normal versus tumoral breast epithelial cell growth regulation. Moreover, vitamin D-related compounds that have been proposed as anti-tumoral drugs were studied for their ability to affect normal and tumoral mammary epithelial cell proliferation and to interfere with the growth-regulatory activity of fibroblasts. Whereas vitamin D compounds inhibited MCF-7 cell growth, they led to a marked stimulation of the proliferation of normal mammary epithelial cells. Moreover, it was shown that the vitamin D analog EB 1089 can block the mitogenic effect of fibroblast-conditioned medium on tumoral but not normal breast epithelial cells. The differential effects of vitamin D compounds on cell proliferation provide further data in favor of the different behaviours of normal and tumoral mammary epithelial cells. The potential therapeutic use of vitamin D derivatives in the treatment of breast cancer is supported by these results but their growth-stimulatory properties on normal epithelial cells cannot be overlooked.

Adenocarcinoma↗
PubMed1999

Preliminary results on the activity of oxaliplatin (L-OHP) in refractory/recurrent non-Hodgkin's lymphoma patients.

BACKGROUND: Many patients with advanced NHL ultimately relapse and require salvage treatment. Oxaliplatin, a diaminocyclohexane (DACH) platinum, has shown a differential spectrum of cytotoxicity with cisplatin, with activity in primary or secondary cisplatin-resistant solid tumors (colon and ovarian cancer). We report the tolerance/activity of this platinum derivate in previously-treated NHL patients. PATIENTS AND METHODS: From July 1988 to February 1994, 22 patients (11 men, 11 women) with recurrent NHL received single-agent oxaliplatin (100-130 mg/m2 i.v. over two hours with antiemetic premedication, q three weeks). All had been previously treated (median number of prior chemotherapy regimens 2, range 1-7) > or = 1 alkylating agent: 22 patients, anthracyclines: 18 patients, cisplatin: four patients, and radiation: 11 patients. Fourteen patients (63%) had progressive disease as best response to their last chemotherapy, and were considered treatment-refractory. All histologies were centrally reviewed in accord with the R.E.A.L. Classification; they were: eight follicular, five MCL, three diffuse large cell, two MALT, one lymphoplasmocytoid, and three other. RESULTS: A total of 144 cycles were administered for a median number of 6 (range 1-30) per patient. The objective response rate was 40% (95%, CI: 21-64), including one CR (MCL) and eight PRs (four follicular, two MCL, two MALT). The median response duration was 27 months (range 5-44). Treatment-related toxicity was limited to grade 1-2 nausea/vomiting and reversible grade 1-2 peripheral neuropathy in most of the patients. CONCLUSION: Oxaliplatin is an active agent in relapsed/refractory NHL, including the MCL type. Its safety profile makes this agent a good candidate for the development of combined salvage regimens. Further phase II studies are needed to confirm these preliminary results.

Adult↗
PubMed1999

Oxaliplatin added to 5-fluorouracil-based therapy (5-FU +/- FA) in the treatment of 5-FU-pretreated patients with advanced colorectal carcinoma (ACRC): results from the European compassionate-use program.

PURPOSE: To provide evidence for the therapeutic efficacy of oxaliplatin (Eloxatin) when given as a 2-6-hour i.v. infusion, alone or in combination with 5-fluorouracil/folinic acid (5-FU +/- FA) in patients with advanced colorectal carcinoma (ACRC) who have failed 5-FU-based therapy. To confirm the safety of the drug and its combination in an extended-access context. PATIENTS AND METHODS: Prescribing physicians were supplied oxaliplatin on a nominative compassionate-use basis, after obtaining informed consent. Europe-wide, 206 ACRC patients in 44 centers received 1168 cycles of chemotherapy with oxaliplatin (80-100 mg/m2 q 2 weeks or 100-135 mg/m2 q 3 weeks) delivered as a short (2-6 hours) i.v. infusion, 177 of them (1026 cycles) receiving oxaliplatin + 5-FU +/- FA. RESULTS: Oxaliplatin added to the 5-FU +/- FA regimens of 111 verified 5-FU-refractory patients (imaging and/or clinical proof of progression under prior 5-FU-based regimen), elicited objective responses in 25 of 98 evaluable patients, (ORR: 25.5%, 95% confidence interval (95% CI: 17-35). The median time to progression was 4.1 months (95% CI: 3.3-5.0) and the median overall survival was 9.6 months (95% CI: 8.2-10.9). Differences in the toxicity profile of the oxaliplatin + 5-FU +/- FA combination appear related to administration modality, dose and schedule of the 5-FU-based regimen. CONCLUSIONS: The addition of oxaliplatin (2-6-hour i.v. infusion) to 5-FU +/- FA regimens is active in ACRC patients with clinical resistance to fluoropyrimidines. The therapeutic index of oxaliplatin + 5-FU +/- FA combinations administered as salvage therapy compares favorably with those reported in recent phase II-III trials involving other new agents or combinations active in 5-FU-refractory ACRC patients.

Adult↗
PubMed1999

Oxaliplatin and paclitaxel combination in patients with platinum-pretreated ovarian carcinoma: an investigator-originated compassionate-use experience.

PURPOSE: Compassionate-use oxaliplatin paclitaxel was assessed for toxicity and efficacy according to clinical platinum resistance status in cisplatin-carboplatin-pretreated advanced ovarian cancer patients. PATIENTS AND METHODS: Thirty-seven patients, retrospectively grouped into four oxaliplatin-paclitaxel dose levels (mg/m2): (DL1: 100/135; DL2: 130-135/135; DL3: 100/160-175; DL4: 130-135/160-175), received oxaliplatin and paclitaxel every three to four weeks. RESULTS: Thirty-one of thirty-seven treated patients were evaluable for activity, with 1 complete and 14 partial responses, (objective response rate: 48%, 95% CI: 31-66). Of 18 platinum-resistant patients 6 responded, and of 13 platinum-sensitive patients, 9 responded. One patient (3%) had two febrile neutropenia episodes, and eight (22%) and eleven patients (30%) had grades 3 and 4 neutropenia, respectively. Six patients (16%) experienced grade 3 peripheral neuropathy. The median response duration was 10.8 months, with a 23-month (range 8-54) median follow-up. Median progression-free and overall survivals were 9 months (95% CI: 7-12), and 25.2 months (95% CI: 12-39), respectively. CONCLUSIONS: The antitumour activity of oxaliplatin-paclitaxel in platinum-resistant ovarian cancer patients accords with experimental data on the agents' lack of cross-resistance. Time-related progression parameters confirm it as a promising salvage treatment option.

Antineoplastic Combined Chemotherapy Protocols↗