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 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Peripheral neuropathies in cancer patients may be caused by compression due to tumor invasion, by radiation injury, or by chemotherapy. Plexopathy may also be caused by non-oncologic conditions such as diabetes mellitus, trauma, and aneurysms, thus adding to the diagnostic difficulty. The most common iatrogenic neuropathies are those caused by vincristine and cisplatin. Vincristine, while causing the least myelosuppression of all the vinca alkaloids, is the most neurotoxic. Cisplatin neuropathy often limits the use of this agent, even in patients whose tumors are responsive to it. Part 1 of this article appeared in January.
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PMID:Peripheral neuropathy in cancer patients: clinical types, etiology, and presentation. Part 2. 216 14

The therapeutic index of adriamycin (ADM) and cisplatin (DDP) combination versus repeated sequences of the more active drug (DDP) was investigated on a murine reticulum cell sarcoma of ovarian origin (M5) implanted i.m. in C57BL/6 mice. The antitumor efficacy of multiple cycles of DDP according to different regimens at a prefixed time (every 7 days) or at tumor regrowth was also evaluated. Our data demonstrate that the ADM-DDP combination did not improve the antitumoral efficacy of DDP as single agent, while repeated cycles of DDP led to a significant increase in the host life span. Differences in therapeutic effect were elicited by the two schedules: the regimen at a prefixed time showed a major effect on local tumor control, although the regimen at tumor regrowth was better tolerated.
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PMID:Schedule-dependent effectiveness of ADM and multiple cycles of DDP on a murine reticulum sarcoma. 218 88

The effect of three second generation platinum complexes on proliferation of tumor cells (HeLa, C6) and nontumor cells (LEP) was studied, and compared with that of cis-DDP. The highest activity, comparable with cis-DDP, was exhibited by oxoplatinum. CBDCA was somewhat less active in this system, but had a greater effect on both lines of tumor cells than on nontumor cells. Cell proliferation was inhibited least of all by CHIP(IV). The differences observed are discussed from the point of view of the structure and oxidation state of the platinum complexes.
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PMID:The effect of second generation platinum cytostatics on mammalian cell proliferation. 218 63

We compared cis-platin (DDP) and its analogue, carboplatin (JM8, CBDCA) in their ability to inhibit spheroid growth. The activities of DDP and JM8 were also compared in an antimetabolic assay for their ability to inhibit (3H)-thymidine incorporation in multicellular tumor spheroids. The spheroids were derived from a squamous cell carcinoma cell line HN-1, originally derived from a tumor of the tongue. To produce equal levels of growth delay in spheroids, carboplatin was required at concentrations approximately 16 times that of DDP. Carboplatin also required much longer incubation periods than DDP to produce equivalent growth delay and proportions of cured spheroids. Reflecting the initial response to chemotherapy, the antimetabolic assay showed that carboplatin was required at higher concentrations and longer exposure times to produce equal inhibition of the nucleotide precursor thymidine. These findings may have implications for the clinical use of these drugs and in particular would support a role for carboplatin in the treatment of squamous cell carcinoma of the head and neck, since total free-drug exposure of patients to carboplatin may be up to 16-fold greater than with DDP, and the clinical side effects of carboplatin have been shown to be well tolerated. However, one must be cautious about applying in vitro data to clinical situations.
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PMID:Effectiveness of cis-platin and carboplatin in the chemotherapy of squamous cell carcinoma grown as multicellular spheroids. 219 88

A modified double-layer Hamburger and Salmon cloning assay was used to test cisplatin and its analogs (spiroplatin, carboplatin and iproplatin) on fresh tumor samples from 63 patients with a variety of non-hematological malignancies. Among them were 18 breast cancers, 17 ovarian cancers and 7 of unknown primaries. Half the patients received prior chemotherapy. Cisplatin regimens were given in 16 cases. When possible, cells were exposed for 1 h to each drug in concentrations of 0.1 microgram/ml and 1.0 microgram/ml for cisplatin and spiroplatin, 1.0 microgram/ml and 10 micrograms/ml for carboplatin and iproplatin. A greater than or equal to 50% cell kill with at least one drug was found in 20 samples including 8 ovarian cancers, 3 breast cancers and 1 unknown primary. A greater than or equal to 70% cell kill was seen in 2 samples with cisplatin, 3 with spiroplatin and carboplatin, and 6 with iproplatin. There was only partial cross-resistance between cisplatin and its analogs. Among 57 paired comparisons of cisplatin with spiroplatin, 2 showed drug sensitivity to cisplatin alone, 6 to spiroplatin alone, and 6 to both. The same sort of observation was made with carboplatin. The lack of cross-resistance between cisplatin and iproplatin was particularly striking: among 53 pairs, 6 were sensitive to cisplatin alone, 8 to iproplatin alone, and 2 to both. About 20% of the samples that were resistant to cisplatin were sensitive to iproplatin. Our data show hints of activity in breast and ovarian cancers with all analogs and suggest that they will achieve clinical antitumor activity similar to that they will achieve clinical antitumor activity similar to that of cisplatin. The in vitro evidence of incomplete cross-resistance between cisplatin and its analogs should be investigated further.
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PMID:Comparative effect of cisplatin, spiroplatin, carboplatin and iproplatin in a human tumor clonogenic assay. 220 31

In osteosarcoma, intraarterial (IA) administration of systemic treatment has been advocated to improve local tumor response preparing for, or even obviating, definitive surgery. Because data from the literature did not unequivocally support the local superiority of IA infusion, a comparative study was started in 1986. Preoperative chemotherapy consisted of 45 mg/m2 of doxorubicin on days 1 and 2; 12 g/m2 of high-dose methotrexate on days 15 and 22; and 3 g/m2 of ifosfamide on days 29, 30, 50, and 51 followed on days 31 and 52 by intravenous (IV) versus IA tourniquet infusion of cisplatin (DDP). A strict randomization of patients was not feasible. A balanced distribution of risk factors was strived for by stratifying and allocating the appropriate patients centrally. The infusion time was prolonged from 1 to 5 hours in the IV group, and the DDP dose was reduced from 150 to 120 mg/m2 in both arms when intolerable ototoxicity became apparent. A multivariate analysis was performed to exclude a bias on the response rates from risk factor distribution and from modifications of DDP infusion time and dosage. The overall fraction of histologic good responders (greater than 90% necrosis) was not found to be different after IA versus IV treatment (34/50 [68%] vs. 41/59 [69%]). Intraarterial instead of IV use of DDP within an aggressive systemic treatment does not seem to improve the local tumor response.
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PMID:Effect of intraarterial versus intravenous cisplatin in addition to systemic doxorubicin, high-dose methotrexate, and ifosfamide on histologic tumor response in osteosarcoma (study COSS-86). 220 24

Attempting to improve local disease control in bulky (greater than 8 cm) primary or recurrent pelvic tumors, 29 patients with squamous cell carcinoma of the cervix (stage II, 4; III, 10; IV, 6; recurrent, 9) were treated with concomitant chemotherapy and split-course hyperfractionated radiation therapy between April 1983 and August 1988. Cisplatin (CDDP) and 5-fluorouracil (5-FU) have been shown to be radiation enhancers; furthermore, CDDP, radiation therapy, and continuous-infusion 5-FU have elicited high local response rates in head and neck squamous cell carcinoma. A pilot study of cyclical week on/week off CDDP, continuous-infusion 5-FU, and hyperfractionated radiation therapy was developed. Radiation was administered at 116 cGy twice daily, Days 1-5, every other week for a median dose of 4600 cGy to a pelvic field, with paraaortic extension if indicated. Concomitant chemotherapy included CDDP 60 mg/m2 IV Day 1 and 5-FU 600 mg/m2 IV continuous infusion for 96 hr following CDDP infusion. Patients received a median of four cycles of combined treatment, and intracavitary or interstitial brachytherapy followed in 21 patients. Local pelvic response was achieved in 29 of 29 (100%): complete response (CR) in 19 of 29 (66%), partial response (PR) in 10 of 29 (34%). Among CR patients 10 of 19 (53%) were without evidence of disease at a mean follow-up of 29 (range 12-76) months. Five-year actuarial disease-free survival among complete responders was 65%. Of the 10 CR patients 2 failed in the pelvis, for a local control rate of 17/19 (89%). Chemotherapy-related and acute radiation morbidity was minimal but 2 patients required surgical correction of radiation injury. Aggressive combination of split-course hyperfractionated radiation therapy with radiation enhancers resulted in promising local control of bulky pelvic tumor, with an acceptable complication rate, in this otherwise very poor prognostic group of patients.
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PMID:Treatment of 29 patients with bulky squamous cell carcinoma of the cervix with simultaneous cisplatin, 5-fluorouracil, and split-course hyperfractionated radiation therapy. 222 42

Cationic lipophilic compounds have a unique cytotoxic mechanism of action which is dependent on mitochondrial-specific localization of these fluorescent dyes. We have demonstrated in vitro that carcinoma cells, which have a higher negative mitochondrial membrane potential than normal cells, have an increased accumulation and retention of two of these compounds. The compounds tested were rhodamine 123 and dequalinium (DECA). After the development of a reproducible murine intraperitoneal (ip) human ovarian cancer model, which maintained the biologic characteristics of the parent cell line, we undertook in vivo evaluation of DECA. Mice with intraperitoneal tumor inoculations were treated with cisplatin, and/or DECA. When compared to cisplatin, a chemotherapeutic agent known to be effective in the treatment of clinical ovarian cancer, DECA was significantly more efficacious and seemed less toxic in the murine model. Cisplatin and DECA used together were possibly synergistic. Cationic lipophilic compounds may prove to be an exciting new class of antineoplastic agents which exploit intracellular, mitochondrial differences between normal cells and cancer cells.
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PMID:Study of the selective cytotoxic properties of cationic, lipophilic mitochondrial-specific compounds in gynecologic malignancies. 222 76

We are analysing the results of 80 patients who underwent surgery during 1983-84 for esophageal cancer. Forty patients who received pre-operative single agent Cis-DDP were grouped under "A" and 40 patients who went for surgery directly were grouped under "B". Twenty-two patients (55%) of Group A showed tumor necrosis. Both groups underwent resection and hand-sewn anastamosis of the esophagus. There were 10 post-operative deaths among 80 resected cases, 9 of them being from anastomatic leak. Cis-DDP has induced negligible side effects. A comparatively high survival rate during early years in patients who responded to Cis-DDP suggests that neoadjuvant chemotherapy might be of value.
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PMID:Neoadjuvant Cis-DDP in esophageal cancers: an experience at a regional cancer centre, India. 223 6

In a prospective pilot study 21 patients with advanced squamous cell carcinoma of the head and neck were treated with polychemotherapy and Hyaluronidase combined with radiation. With the exception of one patient, who refused laryngectomy, all patients were inoperable. Chemotherapy consisted of 5 mg Vindesine on day 1 and 80 mg/m2 Cisplatin on day 2. 200,000 U Hyaluronidase were given by infusion over 20 min prior to Vindesine and Cisplatin. Radiation in fractions of 2 Gy a day was administered 12 times per cycle (day 3-5, 8-12 and 15-18). Treatment was repeated on day 22 and 43. Total radiation dose was 72 Gy. Side-effects were mainly of local character (moderate severe mucositis in 7, mild mucositis in 14 patients). No severe systemic toxicity was seen. Complete remission was noted in 17 out of 21 patients. 16 patients are now a life without progression. 1 patient in complete remission died 5 months after therapy due to pneumonia without evidence of tumor. The mean time of follow up is 16 months (range 3-42). The preliminary results suggest that combined therapy with Vindesine, Cisplatin, Hyaluronidase and Radiation is well tolerable and highly effective against advanced squamous cell carcinoma of the head and neck.
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PMID:[Cisplatin, vindesine and hyaluronidase combined with simultaneous radiotherapy of advanced head and neck tumors]. 223 85


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