摘要:

Interferon-a (IFN-α) has potential dose-limiting neurotoxic side effects when used in cancer therapy. The nature of this neurotoxicity is speculative, and there is no definitive treatment. Because animal studies suggest that IFN-αacts at opioid receptor sites, we gave naltrexone, a long-acting opioid antagonist, to 9 patients who had hematological malignancies and who suffered from IFN-αside effects. Seven of these patients experienced complete or moderate relief of side effects. Five of the patients tested before and during naltrexone treatment showed improvement of cognitive functioning. Two patients could not tolerate naltrexone side effects. This study suggests an intervention against IFN-αside effects and provides support for the role of opioid receptor interaction in IFN-αneurotoxicity.

ISSN:0735-7907    

DOI:10.3109/07357909509024923

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

Laboratory studies have suggested that rapidly alternating chemotherapy and radiation therapy might act synergistically. We undertook this study to evaluate the toxicity and effectiveness of this approach in patients with carcinoma involving the hypopharynx or esophagus. Between 1987 and 1991, we treated 47 patients (23 with carcinoma involving the hypopharynx arid 24 with carcinoma involving the esophagus) by three cycles of chemotherapy (during weeks 1, 4, and 7) rapidly alternating with twice-a-day radiution therapy (during weeks 2, 5, atid 8). Chemotherapy consisted of cisplatin 100 mg/m2and 5-fluorouracil 3–4 g/m2given over 4 days. Radiation therapy consisted of 180–200 cCy twice each day to 2000 ccylcycle, total 6000 cCy over 7 weeks. The histology was squamous cell carcinoma in 44 patients and adenocarcinoma in 3 patients with esophagus cancer. Median follow-up is 2 years (range 1–5 years). The observed survival rate for all 47 patients was 54% at 1 year and 38% at 2 years. Acute toxicity was considerable. Twelve patients (25%) died during therapy porn toxicity, without timor progression, leaving 35 patienrs (18 hypopharynx, 17 esophagus) evaluuble for response. Among the hypopharyngeal patients, 83% had a complete response, 11% had a partial response, and 6% had no response. Among the esophageal patients, 94% had a complete response, and 6% had a partial response. Local control was better for the esophageal patients than the hypopharyngeal patients (98% vs. 52% at 2 years, p = 0.038). The incidence of distant metastases was 25% at 2 years and not significantly different between the two groups. A high rate of local control was achieved, particularly in esophugeal cancer, by delivering chemotherapy and radiation therapy in a rapidly alternating fashion. This was achieved at a considerable cost in terms of toxicity, however. Although our response rates and local control compare favorably with those of other recently published studies of combined modality therapy in esophugus or head and neck cancer, much additional work is required to reduce the toxicity and, in hypopharyngeal cancer, to further improve the local control.

ISSN:0735-7907    

DOI:10.3109/07357909509024924

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

The current study attempted to assess the potential proficiency of radioimmunodetection (RAID) of primary, residual, multicentric, and recurrent breast carcinoma using two radiolabeled murine monoclonal antibodies (MoAbs), anti-human milk fat globulin (HMFG1) labeled with iodine (123I) and anti-carcinoembryonic antigen (CEA) labeled with technetium (99Tc). Thirteen patients with suspicious clinical andlor mammographic primary or recurrent breast carcinoma were studied in a phase I-II prospective, consecutive, nonrandomized, noncontrolled study. Five patients received intravenous infusion with 0.5–2.0 mg anti-CEA MoAb type CYT 380 labeled with99Tc [13–22 millicurie (mCI)] and 8 patients received intravenous infusion with 0.25–1.0 mg anti-HMFG1 MoAb (Unipath, U.K.) labeled with123I (4–17mCI). Both MoAbs used in this study demonstrated ability to bind specifically to breast cancer lesions, resulting in successful RAID in 10 of 12 of studied patients (5 of 5 patients in the anti-CEA-99Tc and 5 of 7 in the anti-HMFG-123I group—accuracy 83.3%). One patient was excluded due to protocol violation. Seven patients had true-positive scans when correlated with surgery (sensitiviv 87.5%) The MoAb scans accurately diagnosed lesions in 3 of the 4 primary invasive breast carcinomas confirmed histologically. Presence of residual carcinoma following wide excision was established in 1 of 2 patients and presence of soft tissue metastases in 3 patients. Three patients had true-negutive scan (specificity 75%): 2 patients presented with suspicious mammographic recurrence postlumpectomy and 1 patient had questionable soft tissue recurrence. One patient with primary breast carcinoma had a false-negative scan and another had a false-positive scan in the presence of fibrosis following lumpectomy and radiation therapy. No adverse reactions were noted in the patients studied. RAID findings were confirmed by immuno-histochemistry in 6 of 9 cases studied. Our data suggest that radiolabeled MoAbs used in this study are potentially useful diagnostic agents for evaluation of primary or recurrent breast carcinoma, particularly in the areas where conventional methodology is limited.

ISSN:0735-7907    

DOI:10.3109/07357909509024925

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

Interleukin-2 (IL-2) is a lymphokine with pleiotropic activities on the immune system. When administered in vivo, besides inducing unrestricted tumor cytotoxicity, it is also responsible for the secondary release of other lymphokines, such as IL-1, TNF, and marrow growth factors, which may mediate some of the clinical toxicities (as well as therapeutic effects) seen during IL-2 immunotherapy. Among the clinical effects of IL-2, we previously reported thrombocytopenia and IL-2-induced in vitro inhibition of platelet aggregatiori accompanied by rapid secretion of alpha-granule components such as platelet factor 4 (PF4) and beta-thromboglobulin. Platelets coiistitute one of the largest storage forms of TGFβ. Preliminary evaluation of this factor in patients receiving IL-2 had indicated that plasma TGFβactivity increased in cancer patients following IL-2 therapy. We report a more detailed study of the quantitation of TCFβactivity, in the plasma of 23 cancer patients treated with IL-2 immunotherapy. Of interest, we found that although elevation of the bioactive form of TGFβoccurred in most patients during IL-2 therapy, it was significantly higher in patients with clinical regression of tumor (p =,004). In the first 2 weeks of therapy increase of plasma TGFP activity appeared to correlate with a decrease of platelet counts, suggesting that the factor may derive from the storage form of TGFβcontained therein.

ISSN:0735-7907    

DOI:10.3109/07357909509024926

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

Bioflavonoids, extracted from flower petals, were examined for their growth inhibitory effect on cells in culture. They were found to significantly suppress the growth of the cultured cells. Anthocyanins tended to show greater inhibitory effect than other flavonoids. Commercially synthesized or purified aglycones of flavonoids were also studied for their suppression of tumor cells. The anthocyanins were more effective than other flavonoid aglycones, although the aglycones were easily inactivated under the culture conditions.

ISSN:0735-7907    

DOI:10.3109/07357909509024927

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

Interferons (IFNs) augment the effect of some antitumor agents, including cisdiamminedichloroplatinum(II) (cDDP), in experimental systems. The effect of human recombinant interferon-alpha2b(rIFNα) on the cDDP-dependent growth delay of a human non-small cell lung cancer established as a xenograft in nude mice (NX002) has been investigated. IFN (105IU/mouse, s.c.) as a single agent had no effect on the growth of the xenograft. cDDP (4.2 mg/kg, i.p.) caused a specific growth delay of 0.42, and this delay was significantly enhanced (to 1.08) by concomitant dosing with the otherwise inactive IFN. Possible mechanisms for this supra-additive relationship between IFN and cDDP have been investigated: increased intratumoral accumulation of platinum was seen at late time points (maximally at 36 hr) during the pharmacokineticβ-phase of cDDP elimination from the plasma of the nude mice. Tumor: plasma platinum concentration ratios at 36–48 hr indicated significantly increased accumulation of platinum in tumors from IFN-treated mice compared to controls (p<0.05). Scheduling experiments suggest that this IFN-mediated effect can persist for 4 hr. These differences may account for the enhanced antitumor activity of cDDP when coadministered with IFN.

ISSN:0735-7907    

DOI:10.3109/07357909509024928

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

Enhancement of radiation injury to the skin and mucous membranes has been observed with a number of chemotherapeutic agents. A 32-year-old woman with metastatic breast cancer received local radiation therapy to the lumbosacral area. Six weeks later, systemic edatrexate therapy was initiated and a localized painful erythema with edema and a vesicular eruption occurred over the previous site of radiation therapy. Physicians should be aware that edatrexate can cause radiation recall, and that careful use of anti-inflammatory agents may allow continued chemotherapy treatment.

ISSN:0735-7907    

DOI:10.3109/07357909509024929

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

We observed leukoencephalopathy in I patient, and progressive dementia in another, during the administration of 5-fluorouracil (5-FU) and levamisole. A retrospective search, among 80 other patients with resected colorectal cancer receiving 5-FU and levamisole as adjuvant therapy, 166 resected malignant melanoma patients receiving adjuvant levamisole, and 254 advanced colorectal cancer patients receiving 5-FU often combined with leucovorin, for other cases of encephalopathy was negative. The frequency of this neurotoxicity is low (about 2% of patients receiving 5-FU and levamisole), but it appears specific for this combination of drugs. The lack of complete reversibility on stopping the drugs is worrisome, as this therapy is used to improve the curability of resected colon cancer.

ISSN:0735-7907    

DOI:10.3109/07357909509024930

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

ISSN:0735-7907    

DOI:10.3109/07357909509024931

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

ISSN:0735-7907    

DOI:10.3109/07357909509024932

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor