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PubMed2000

The effect of fasting or desmopressin before treatment on the concentration of mitomycin C during intravesical administration.

OBJECTIVE: To evaluate two methods of reducing the urine output during treatment (the most easily manipulated variable) in patients undergoing intravesical instillation with mitomycin C, where the concentration-time curve also depends upon dose, diluent volume, residual urine volume, and drug absorption and degradation. PATIENTS AND METHODS: The study comprised 20 consecutive patients undergoing a course of six weekly instillations of mitomycin C (40 mg in 40 mL for 1 h) for superficial bladder carcinoma. Urine production during treatment was calculated by adding the voided volume and ultrasonographically measured residual urine after treatment, and subtracting 40 mL; the patient's bladder was emptied before instillation. Before the first and second visit the patients were asked to drink normally. Before the third and fourth visit patients fasted for 6 h before treatment. For the fifth and sixth visit the patients had not fasted, but 200 microg of desmopressin was given orally 1 h before instillation. Any urinary side-effects were graded on a four-point scale. RESULTS: There were 17 patients with complete data; one patient failed to take desmopressin, one had detrusor instability and one developed chemical cystitis. The mean (SD) urine production in unprepared patients was 209 (123) mL, which decreased to 143 (80) mL (P = 0.039, t-test) after fasting and 103 (51) mL (P < 0.001) with desmopressin. This equates to a 20% increase in mean intravesical drug concentration with fasting and a 38% increase with desmopressin. Urinary side-effects were graded as mild in each group. CONCLUSION: Unprepared patients produce variable and often substantial volumes of urine during intravesical chemotherapy. There was a significant reduction in urine output after fasting or by administering desmopressin before instillation. These measures increase the area under the concentration-time curve for mitomycin C and potentially increase the efficacy of treatment.

Administration, Intravesical↗
PubMed2001

Mitomycin C: a clinical update.

Mitomycin C was reviewed in this journal 25 years ago and an update of its clinical usefulness is appropriate. The current review is based on representative publications covering clinical trials performed throughout the world. Single agent activity in each of the major neoplastic diseases has been reassessed when possible and the most important combinations evaluated. It is concluded that mitomycin C has a definite place in the treatment of localized bladder cancer, is active, but needs to be redefined, in the context of newer regimens for breast, head and neck, and non-small cell lung cancers, is active in, but is being displaced by, other drugs in cervical, gastric and pancreatic cancers, and is probably no longer of therapeutic value in colon cancer. It is also recognized that as many newer treatments have clinical success, the therapeutic role of mitomycin C will require continuing re-investigation.

Antibiotics, Antineoplastic↗
PubMed2000

Phase III randomized trial comparing moderate-dose cisplatin to combined cisplatin and carboplatin in addition to mitomycin and ifosfamide in patients with stage IV non-small-cell lung cancer.

A phase III randomized trial was conducted in patients with metastatic NSCLC, to determine if, in association with mitomycin (6 mg m(-2)) and ifosfamide (3 g m(-2)), the combination of moderate dosages of cisplatin (60 mg m(-2)) and carboplatin (200 mg m(-2)) - CarboMIP regimen - improved survival in comparison with cisplatin (50 mg m(-2)) alone - MIP regimen. A total of 305 patients with no prior chemotherapy were randomized, including 297 patients assessable for survival (147 in the MIP arm and 150 in the CarboMIP arm) and 268 patients assessable for response to chemotherapy. All but eight (with malignant pleural effusion) had stage IV disease. There was a 27% (95% CI, 19-34) objective response (OR) rate to MIP (25% of the eligible patients) and a 33% (95% CI, 24-41) OR rate to CarboMIP (29% of the eligible patients). This difference was not statistically significant (P = 0.34). Duration of response was not significantly different between both arms. There was also no difference (P = 0.67) in survival: median survival times were 28 weeks (95% Cl, 24-32) for MIP and 32 weeks (95% Cl, 26-35) for CarboMIP, with respectively 1-year survival rates of 24% and 23% and 2-year survival rates of 5% and 2%. The main toxicities consisted in emesis, alopecia, leucopenia and thrombocytopenia, that were, except alopecia, significantly more severe in the CarboMIP arm. Our trial failed to demonstrate a significant improvement in response or survival when patients with metastatic NSCLC were treated, in addition to ifosfamide and mitomycin, by combination of moderate dosages of cisplatin and carboplatin instead of moderate dosage of cisplatin alone. The results support the use of a moderate dose (50 mg m(-2)) of cisplatin in combination with ifosfamide and mitomycin for the chemotherapy of this disease.

Adult↗
PubMed2001

Apoptosis and epithelial phagocytosis in mitomycin C-treated human pulmonary adenocarcinoma A549 cells.

Fate of human cancer cells damaged by mitomycin C was investigated by electron microscopy. In a monolayer culture of pulmonary adenocarcinoma A549 cells, the antitumor drug mitomycin C induced dilation of the smooth endoplasmic reticulum and Golgi apparatus. Simultaneously, the myelin figures, autophagosomes and dense tonofilament bundles were formed in the cytosol. Nuclear changes also included nucleolar condensation, as well as the disappearance of the karyosomes and thinned marginal heterochromatins. These nuclei came to be rigid and densely chromatic, finally resulting in apoptosis. There was no alteration in the mitochondria or rough endoplasmic reticulum. Meanwhile, some remaining intact A549 cells extended their cytoplasm toward detached cells and engulfed them. These results indicate that mitomycin C induces apoptosis in A549 cells and concurrently stimulates epithelial phagocytotic activity against their own damaged cells.

Adenocarcinoma↗
PubMed2001

[Treatment of 9 squamous epithelial carcinoma in situ lesions of the conjunctiva (CIN) with mitomycin C eyedrops in cytological and DNA image cytometric control].

BACKGROUND: Conjunctival intraepithelial neoplasia (CIN) is a frequent conjunctival tumor. Following excision alone recurrences are frequent. An effective postsurgical recurrence prevention is therefore highly desirable. In this study we aimed to evaluate the effectivity of postsurgical chemotherapy of conjunctival squamous cell carcinoma in situ (CIN) with mitomycin C eyedrops. We introduced the otherwise established diagnostic tools of cytology and DNA-image-cytometry to the diagnosis and therapy-monitoring of CIN. PATIENTS AND METHODS: We treated 9 patients with CIN. For diagnosis the results of cytology and cytometry of presurgically obtained brush smears were compared with the histologic evaluation of the excised tissue. After surgery, we administered topical chemotherapy with mitomycin C eye drops 0.02% (MMC). Conjunctival brush smears were again evaluated by cytology and DNA-image-cytometry for postsurgical therapy monitoring. RESULTS: The clinical diagnosis of CIN was fully confirmed by cytology, DNA-image-cytometry and histology respectively in 7 patients. In one patient, the results of the applied diagnostic methods differed in results: Histologic evaluation indicated a moderate dysplasia but DNA-image-cytometry showed significant DNA-aneuploidy unequivocally indicating neoplasia like squamous cell carcinoma. In another patient the preoperatively obtained conjunctival brush smears could not properly analyzed by cytometry but clinical diagnosis was confirmed by histology. MMC-therapy was well tolerated except for a self-limited conjunctivitis. A complete remission of CIN was obtained in 8 of 9 patients (89%) who were free of CIN recurrences during a follow-up period of 27.2 months (11-48). Only one patient suffered from a recurrence 14 months after surgery and after 2 MMC-cycles. CONCLUSION: Adjuvant topical mitomycin C appears to be effective in the prevention of recurrences of conjunctival CIN after surgical removal. Our results indicate that at least 4 cycles of topical MMC are required to prevent local recurrences in the long term. Cytology and DNA-image cytometry are highly sensitive and specific methods for diagnosis and therapy monitoring of conjunctival squamous cell carcinoma in situ (CIN).

Adult↗
PubMed1998

[Mitomycin C in treatment of conjunctival melanoma and primary acquired melanosis].

BACKGROUND: Since 1995 we have used Mitomycin C additionally in the treatment of conjunctival melanoma and primary acquired melanosis. METHODS: We report on the therapy results of 14 patients suffering from pigmented conjunctival lesions (malignant melanoma 9 and primary acquired melanosis 5). After local excision, cryotherapy or irradiation all patients received one eye drop Mitomycin C (0.02%) four times daily for four to six weeks. RESULTS: We observed regression of the pigmentations in 11 cases after median follow up of 13.1 months. In one patient there was no change. Two cases showed progression with tumefaction. There were no adverse reactions except conjunctival hyperemia during therapy. CONCLUSIONS: Topical administration of Mitomycin C may be useful in the treatment of pigmented conjunctival lesions. Longer follow-up periods are necessary.

Adolescent↗
PubMed1996

[Incidence of recurrence after primary pterygium excision, phototherapeutic keratectomy with the ArF:Excimer laser and local mitomycin C administration].

BACKGROUND: In this clinical trial the recurrence-rate after primary pterygium-excision, phototherapeutic keratectomy with the ArF:excimerlaser and local application of mitomycin C should be estimated. MATERIAL AND METHODS: Forty eyes of 38 patients underwent primary pterygium-excision using a bare-sclera technique. All patients underwent phototherapeutic keratectomy (PTK) with the ArF:excimerlaser of the wound region. Postoperative all patients were treated with mitomycin C 0.02% twice daily for four days and for 4-6 weeks with a combination of gentamycin and dexametason eye drops triple a day. Minimum follow-up was 24 month (median 41 month). RESULTS: Two eyes developed a recurrence after 12 and 28 month respectively. The overall recurrence rate was 5% (corneal recurrence 2.5%). One patient developed a minute granuloma in the area of the excision. There were no other complications during the follow-up. CONCLUSIONS: The excision of pterygium using the bare-sclera technique, phototherapeutic keratektomy und local application of mitomycin C 0.02% eye drops is a safe method with a low recurrence-rate. All recurrences occured after more than one year postoperatively.

Adult↗
PubMed1994

[Experiences with mitomycin C].

BACKGROUND: Recently, encouraging results with the use of Mitomycin C in trabeculectomy have been reported. PATIENTS: We used Mitomycin C (0.028%) during trabeculectomy in 72 eyes of 68 patients. Forty-one eyes have already been controlled during 6 months and 19 eyes during 9 months after the surgery. RESULTS: The mean intraocular pressure after 6 and 9 months was respectively 13 +/- 8 mm Hg and 13 +/- 10 mm Hg. The difference between these results and the preoperative values (27 +/- 9 mm Hg) were statistically significant after 6 and 9 months (p < 0.001). Despite frequent choroidal detachments (20 eyes), the visual acuity recovered during the follow-up to the preoperative values. CONCLUSIONS: In patients with uncertain prognosis for the intraocular pressure after trabeculectomy, the intraoperative application of Mitomycin C seems to improve considerably the operative success rate.

Adult↗
PubMed1994

[Adjuvant treatment with mitomycin eyedrops after pterygium excision: Ticino experience].

AIM OF THE STUDY: Prospective pilot-study in the canton of Ticino to evaluate the prevention of recurrence of pterygium after excision and mitomycin drops. METHODS: Mitomycin 0.02% drops have been used from 6 to 10 days after 24 cases of corneoscleral excision of the pterygium. RESULTS: After a mean observation time of 13 months, we did not see any recurrence. The vision was improved in 8 eyes over 21, was unchanged in 15 eyes and deteriorated in 1 eye due to unrelated causes. In two cases we observed a thinning of 0.3 mm deep over 1 mm2 of the sclera. CONCLUSIONS: The rate of recurrence after excision of the pterygium and followed by instillation of mitomycin drops is lower than the other described treatments. However, complications described in literature, yet not observed in our own study, underline the necessity of a prolonged perspective study.

Adult↗
PubMed1995

Distortion after monofunctional alkylation by mitomycin C of a dodecamer containing its major binding site.

The structural distortions of the duplex dodecamer d(ATTAACGTTAAT)2 monofunctionally alkylated by mitomycin C have been studied by the use of chemical probes reactivity and resonance Raman spectroscopy. This sequence contains the 5'-ACGT sequence for which mitomycin C was determined to present the best affinity (S. Kumar, R. Lipman, and M. Tomasz, Biochemistry 31, 1399 (1992)). Raman spectroscopy as well as osmium tetroxyde reactivity indicate that the distortion of the double helix structure is located around the central CG bases. Mitomycin C reacts exclusively with the 2-amino group of guanine and this binding does not disrupt the inter bases H-bonds, as indicated by chloroacetaldehyde reactivity. Although resonance Raman spectroscopy does not allow the handedness of the monoalkylated CG/GC sequence to be determined, it indicates a similarity between the base stacking and that which would be observed for alternating purine/pyrimidine sequences at high salt concentration.

Acetaldehyde↗
PubMed2004

Salvage chemotherapy with mitomycin, docetaxel, and irinotecan (MDI regimen) in metastatic pancreatic adenocarcinoma: a phase I and II trial.

BACKGROUND: This study evaluates the maximum tolerated dose (MTD) and activity of mitomycin, docetaxel, and irinotecan (MDI) regimen on metastatic pancreatic adenocarcinoma, previously treated with gemcitabine-containing chemotherapy. PATIENTS AND METHODS: Patients with less than 76 years, Karnofsky performance status > or = 60, and adequate bone marrow, kidney, and liver function were eligible for this trial. Treatment consisted of mitomycin 6 mg/m2 day 1, docetaxel and irinotecan on days 2 and 8 with escalating doses, every 4 weeks. Dose levels were level 1:30 and 70 mg/m2; level 2:30 and 100 mg/m2; level 3:30 and 85 mg/m2; and level 4:35 and 85 mg/m2. Dose-limiting toxicity (DLT) was defined as grade 4 neutropenia > 7 days, febrile neutropenia, grade 4 thrombocytopenia, nausea and vomiting, or diarrhea, grade > or = 3 nonhematological toxicity, or failure to recover to grade < or = 1 toxicity by day 43, occurring during the first cycle of chemotherapy. RESULTS: Between September 2001 and October 2002, 15 eligible patients, three of whom had been previously treated with two lines of chemotherapy, received 33 cycles of MDI. Toxicity consisted of grade 3 to 4 neutropenia in 23% of cycles, fatigue, diarrhea, and vomiting in 10% of cycles, and one toxic death. DLT was observed in 2 of 6 level 2 patients (one toxic death and one grade 3 fatigue), and 2 of 3 level 4 patients (one neutropenic fever and one grade 3 fatigue). Thirteen patients were assessable for response. No objective response was observed among patients treated with MTD or higher doses. Three patients had stable disease; all other patients had progressive disease. The median time to tumor progression and median survival was 1.7 and 6.1 months, respectively. CONCLUSION: The MTD was mitomycin 6 mg/m2 day one, and docetaxel 30 and irinotecan 85 mg/m2 days 2 and 8. This regimen is inactive in metastatic pancreatic cancer.

Adenocarcinoma↗
PubMed1968

Different lethal effects of mitomycin C and actinomycin D during the division cycle of HeLa cells.

The lethal actions of mitomycin C and actinomycin D were followed during the division cycle of HeLa cells. The cells were most susceptible to a 2 hr pulse of mitomycin C during the G(1) phase, whereas their sensitivity to actinomycin D was most pronounced in the S phase. Posttreatment of the cells with acetoxycycloheximide, a potent inhibitor of protein synthesis, increased the survival (colony-forming ability) of cells treated with mitomycin C but had very little effect on the survival of cells treated with actinomycin D. The significance of these findings is discussed.

Cell Division↗
PubMed2006

Effect of diode laser application with G-probe on ocular hypotony after trabeculectomy with mitomycin-C.

OBJECTIVE: The aim of this study was to assess the feasibility of a new technique to treat overfiltering blebs leading to hypotony after penetrating glaucoma surgery. BACKGROUND: There is no previous report on diode laser application with G-probe on ocular hypotony consequent to trabeculectomy with adjunctive mitomycin-C. METHODS: This clinical trial was conducted on eight eyes of eight patients with hypotony after trabeculectomy with adjunctive mitomycin-C. Ten to 12 diode laser (810 nm) spots were applied by G-probe over the bleb area with 2000-2500 mw power and for 1500-2000 msec duration; if the bleb was thin, the laser was applied on its border. RESULTS: The mean age of patients was 29.1 +/- 12.4 years; two of them were female. Mean preoperative and postoperative intraocular pressure (IOPs) were 4.3 +/- 1.5 and 10.1 +/- 3.4 mm Hg, respectively (p = 0.017). Although the IOP increased in seven eyes (87.5%), the visual acuity increased > or =1 line in four (50%), remained stable in three (37.5%), and decreased 1 line in one (12.5%) after an average follow-up of 4 months. All of the blebs were notably smaller and pigmented. No complications occurred other than the need to start Timolol eye drops in one eye for controlling IOP and peaked pupil in two others. CONCLUSION: Diode laser application with G-probe appears to be a useful modality of treatment for ocular hypotony and overfiltering blebs resulting from trabeculectomy with mitomycin-C.

Adolescent↗
PubMed1994

Cisplatin, doxorubicin, mitomycin C, and 5-fluorouracil for the treatment of metastatic non-small cell lung cancer. Limited activity of an aggressive chemotherapy regimen.

We conducted a Phase II study to determine the efficacy of cisplatin, doxorubicin, mitomycin C, and 5-fluorouracil in patients with untreated non-small cell lung cancer. Patients were accrued through the Connecticut Oncology Association (COA), an organization composed of community and university oncologists. Thirteen COA oncologists enrolled 30 patients over 12 months and 26 were eligible for the final analysis. Patients received cisplatin 75 mg/m2, doxorubicin 30 mg/m2, mitomycin C 6.5 mg/m2, and 5-fluorouracil 750 mg/m2 on day 1. The treatment was repeated every 4 weeks, with mitomycin C given during the first 3 cycles and then every other cycle. There were 5 (19%) partial responses, lasting 1.3-7.3 months. The median time to progression was 10.3 months (0.3-12.5 months). Median survival was 7.5 months (0.3-34 months). The major toxicities were related to myelosuppression and there was one septic death. This study demonstrates the limited efficacy of an aggressive regimen using "active" agents in patients with advanced non-small cell lung cancer.

Adult↗
PubMed1995

Interim results on a randomized trial of mitomycin C in combination with orchidectomy for newly diagnosed metastatic prostate cancer.

The interim results of a randomized trial comparing orchidectomy alone versus orchidectomy and mitomycin C in 178 newly diagnosed metastatic prostate cancer patients are presented. Of 148 evaluable patients 75 were treated with orchidectomy alone and 73 received adjuvant intravenous mitomycin C. Mean time to progression was 15 months in the orchidectomy group versus 14 months in the mitomycin C group. Interim analysis did not demonstrate a favorable effect of the combination with this chemotherapeutic agent compared to orchidectomy alone (P = .45).

Aged↗
PubMed1997

In vitro toxicity studies with mitomycins and bleomycin on endothelial cells.

Pulmonary side effects are increasingly observed as dose-limiting toxicity (DLT) of cancer treatment. The available preclinical models have a limited predictive value for lung toxicity in humans. We have attempted to elucidate potential mechanisms involved in these reactions, by studying the effects on cells, possibly involved in these reactions after in vitro exposure to drugs with known lung toxic effects. We have investigated the effects of bleomycin (BLM), mitomycin C (MMC), KW-2149 and its two known metabolites, M16 and M18, on oxygen radical production by granulocytes, on cytokine production: interleukin (IL)-6, transforming growth factor (TGF)-beta, tumor necrosis factor (TNF)-alpha by a human macrophage cell line (THP-1), by human endothelial cells (HVEC and HMEC) and a human colorectal cancer cell line (DLD-1), and on the cytotoxicity on endothelial cells in both confluent and non-confluent culture. The generation of oxygen radicals by normal and pre-stimulated granulocytes was not increased after preincubation with any of the drugs, at the concentrations tested. None of the cytokines (IL-6, TNF-alpha or TGF-beta) was found significantly increased in culture medium after exposure to any of the mitomycins. This was in contrast with the effect of BLM incubation, causing a rise in TGF-beta concentration. Both types of endothelial cells showed a dose-dependent, exposure duration-dependent, proliferation inhibition for all agents tested. This inhibitory effect was clearly proliferation dependent as shown by the increased inhibition in semi-confluent as opposed to confluent endothelial cell cultures. Both mitomycins tested were more cytotoxic than BLM to both confluent and proliferating endothelial cells.

Antibiotics, Antineoplastic↗
PubMed2002

Combined surgery, cryotherapy, and mitomycin-C for recurrent ocular surface squamous neoplasia.

PURPOSE: To report the outcome of combined excision, cryotherapy, and antimetabolite treatment of recurrent ocular surface squamous neoplasia. METHODS: The patients with recurrent ocular surface squamous neoplasia were treated by excision of lesion, cryotherapy of limbus, and conjunctival margin followed by 0.02% Mitomycin C application at the time of surgery. Patients have been followed up for at least 1 year. RESULTS: A total of five eyes of five patients with recurrent ocular surface squamous neoplasia were treated by combined excision, cryotherapy, and Mitomycin C. Histopathologic diagnosis included invasive squamous cell carcinoma in four cases and squamous dysplasia in one case. No recurrences have been noted for a follow-up period of more than 1 year now. CONCLUSION: Combining excision with cryotherapy and Mitomycin C application at the time of surgery is a very effective therapy for recurrent ocular surface squamous neoplasia. It is relevant for cases in large, poor countries where patients present late and are less likely to come for follow-up care.

Adult↗
PubMed2002

Excimer laser phototherapeutic keratectomy retreatment of anterior basement membrane dystrophy and Salzmann's nodular degeneration with topical mitomycin C.

PURPOSE: To report a case of excimer laser phototherapeutic keratectomy retreatment of anterior basement membrane (ABM) dystrophy and Salzmann's nodular degeneration with a single intraoperative application of topical mitomycin C (0.02%). METHODS: Case report. RESULTS: A 91-year-old woman underwent excimer laser phototherapeutic keratectomy (PTK) in the left eye for ABM dystrophy and Salzmann's nodular degeneration causing decreased visual acuity (VA), ocular irritation, and recurrent erosions. Slit-lamp examination of both eyes revealed diffuse ABM dystrophy changes with mild to moderate subepithelial and anterior stromal haze and scarring involving the visual axis. The PTK treatment was preceded by a superficial keratectomy with a blade. The excimer laser was set for a 6-mm circular ablation zone with a treatment depth of 5 microm. The cornea remained clear for several months. Six months after surgery, the patient presented with difficulty reading and VA of 20/70. Slit-lamp examination of the left eye revealed recurrent Salzmann-type nodular degeneration inferior to the visual axis. A treatment course of topical steroids was not successful. She underwent another superficial keratectomy with a blade and PTK treatment (same laser parameters as the first procedure) with a 2-minute application of 0.02% mitomycin C on a cellulose sponge. The surgery proceeded without complications. On postoperative day 7, she presented with a healed epithelium and faint anterior stromal haze. Best-corrected visual acuity was 20/50, which is her best-expected VA. Six months after the procedure, the cornea revealed no signs of recurrence. CONCLUSION: The use of topical mitomycin C in conjunction with PTK may prevent recurrence of Salzmann's nodular degeneration.

Aged↗