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Interstitial pneumonia from mitomycin.

Pulmonary disease has been associated with several chemotherapeutic agents but has not been reported in patients receiving the alkylating agent mitomycin (Mutamycin). We describe here the cases of three patients who developed interstitial pneumonia while receiving mitomycin therapy. Their clinical features including dyspnea, cough, and occasionally fever; reticular infiltrates were seen on chest roentgenogram. Histologically, diffuse alveolar septal edema, mononuclear-cell interstitial infiltrates, hypertrophy of alveolar lining cells, and alveolar septal collagen deposition were characteristic. Treatment with corticosteroids was associated with a rapid therapeutic response in all three patients.

Female↗

Comparative studies on the antitumor effect on intravenous administration of carbazilquinone and mitomycin-C.

Comparison between Carbazilquinone and Mitomycin-C, both of which contain aziridinyl, carbamoyloxy, and quinonyl groups, was made for their therapeutic effect upon intravenous administration. Although both agents exhibited a significant effect on plasmacytoma X5563 in C3H/He mice to a similar extent, Mitomycin-C was not as effective on lympholeukemia L-1210 and on the lung metastasis of Ehrlich carcinoma in (C57BL/6 X DBA/2)F1 (BDF1) mice as was Carbazilquinone. Possible interpretations regarding this discrepancy are discussed.

Animals↗

Results of medical management and mitomycin C-augmented excisional bleb revision for encapsulated filtering blebs.

BACKGROUND AND OBJECTIVE: To assess the outcome of medical management and mitomycin C (MMC)-augmented excisional bleb revision (EBR) for encapsulated filtering blebs. PATIENTS AND METHODS: The author conducted a retrospective study of 503 patients who had undergone trabeculectomy performed over a 5 year period, followed up for at least one year, in order to identify the encapsulated filtering blebs. Mitomycin C-augmented (0.4mg/ml for 3 minutes) EBR was performed in cases of failed medical therapy for managing encapsulated blebs consisting of antiglaucoma medications, topical steroids, and digital compression. RESULTS: An encapsulated bleb developed in 18 eyes (3.6%) of 503 patients. Identification of bleb encapsulation occurred at a mean follow-up time of 24.2 +/- 10.4 days after surgery. The mean intraocular pressure (IOP) at that point was 30.4 +/- 11.7 mmHg in the affected eyes. Fifteen (83.3%) of 18 eyes responded to conservative management and 3 eyes (16.7%) required MMC augmented EBR. The mean IOP reduced from 30.4 +/- 11.7 mmHg to 14.2 +/- 4.2 mmHg after a mean follow-up of 37.6 +/- 11.4 months in the conservative management group, while it reduced from 37.3 +/- 23.4 mmHg to 12.0 +/- 4.4 mmHg after a mean follow-up of 42 +/- 6 months in the surgically treated group. None of the surgically treated eyes developed MMC-related complications. CONCLUSION: Conservative management is very effective in the treatment of encapsulated filtering blebs. The intraoperative use of MMC is a safe and effective adjunct in EBR in cases where conservative management has failed.

Follow-Up Studies↗

The effect of mitomycin-C on the healing process in rabbit extraocular muscle surgery.

BACKGROUND AND OBJECTIVE: One of the most serious complications following extraocular muscle surgery is formation of postoperative adhesions that may result in restrictive ocular motility dysfunction. The effect of mitomycin-C (MMC) on postoperative wound healing in extraocular muscle surgery was investigated. MATERIALS AND METHODS: Sixteen albino rabbits (24 eyes) were used and anesthetized with ketamine and xylazine. These rabbits were divided into 3 groups; (1) control group (balanced salt solution (BSS) exposure for 5 minutes), (2) Group 1 (0.5 mg/ml MMC exposure for 1 minute) and (3) Group 2 (0.5 mg/ml MMC exposure for 5 minutes). After 3 mm recession of superior rectus muscle, MMC or BSS was applied using Weck-Cel sponge (Solan, Jacksonville, FL). The reduction of fibroblast and collagen fiber proliferation were evaluated histopathologically with light microscope at 1, 2, 4 and 8 weeks after operation. We also evaluated the amount of basic fibroblast growth factor (bFGF) by immunohistochemical study at the same time. RESULTS: Histopathologically, there was a more significant reduction of fibroblast and collagen fiber proliferation in Group 1 and 2 than the control group. Immunohistochemically, Group 1 and 2 showed lesser expression of bFGF than the control group. But, there was no difference between Group 1 and 2. CONCLUSIONS: Topical intraoperative application of mitomycin C in extraocular muscle surgery may reduce postoperative adhesions.

Animals↗

Phase I study of oral mitomycin C.

This study demonstrates that the gastrointestinal absorption of oral mitomycin C is variable and that myelosuppression correlates most closely with the peak serum concentration. The probable maximal-tolerated dose of oral mitomycin C is 45-50 mg/m2.

Administration, Oral↗

Mitomycin-C in combined or two-stage procedure trabeculectomy followed by penetrating keratoplasty.

PURPOSE: To evaluate the efficacy and safety of application of mitomycin-C (MMC) in combined and separate trabeculectomy and penetrating keratoplasty for the treatment of coexisting corneal disease and glaucoma. METHODS: A retrospective evaluation of 11 eyes of 10 patients was conducted. A combined trabeculectomy with MMC and penetrating keratoplasty procedure was performed in eight eyes (group 1), and keratoplasty was performed after a previous trabeculectomy with MMC in three eyes (group 2). RESULTS: In group 1, seven of the eight eyes had controlled intraocular pressure (IOP) and clear corneal graft at the end of the follow-up period (range, 5-60 months; mean duration, 16.7 months). In group 2, all three eyes had controlled IOP at the end of the follow-up period (range, 4-30 months; mean duration, 14 months); two of these patients had clear corneal grafts, and graft failure occurred in the remaining patient. Complications included transient flat anterior chamber and corneal epithelial defects, each of which occurred in a single eye in group 1, and progressive cataract, which occurred in a single eye in group 2. CONCLUSION: Mitomycin-C was found to be safe and efficient in the present series, controlling IOP in 10 of 11 eyes (91%) with coexisting corneal disease and glaucoma. The transplanted corneas remained clear in 9 of 11 eyes (82%). Complications related to MMC included a reversible epithelial defect that occurred in one eye.

Adolescent↗

Extensive gastrectomy and carbon-adsorbed mitomycin C for gastric cancer with peritoneal metastases. Case reports of survivors and their implications.

BACKGROUND/AIMS: Extensive gastrectomy, defined as gastrectomy with complete omentectomy and extended lymphadenectomy, improves the survival of gastric cancer patients with peritoneal metastases, even though peritoneal metastasis is considered the end-stage of cancer. MMC-CH, a new dosage formulation of mitomycin C, extended the survival of rabbits with peritoneal carcinomatosis as compared to aqueous mitomycin C. METHODOLOGY: We retrospectively reviewed 114 patients who underwent gastrectomy for gastric cancer with peritoneal metastases. RESULTS: Six patients survived for more than 5 years after the therapy out of 63 patients treated with MMC-CH therapy and extensive gastrectomy for gastric cancer with P1, i.e., metastases to the adjacent peritoneum but no metastasis to the distant peritoneum, or P2, i.e., a few metastases to the distant peritoneum. However, there were no 5-year survivors in patients with P3, i.e., numerous metastases to the distant peritoneum, or in patients treated with incomplete omentectomy, limited lymphadenectomy and no MMC-CH therapy. CONCLUSIONS: The results imply that gastric cancer patients with P1 or P2 have a possible chance to survive more than 5 years when treated with MMC-CH therapy and extensive gastrectomy.

Adenocarcinoma↗

[The effect of heterogeneous scleral transplantation on hypotony after filtration surgery of glaucoma with mitomycin C].

OBJECTIVE: The study was designed to observe the effect of heterogeneous scleral transplantation in treatment of hypotony after filtration surgery of glaucoma with mitomycin C. METHOD: 7 patients (8 eyes) with hypotony after filtration surgery of glaucoma with mitomycin C were treated by heterogeneous scleral transplantation. RESULTS: The post-operative follow-up periods ranged from 3 to 19 months (mean 7.75 +/- 5.37 months). Postoperatively, the visual acuity was increased in 5 eyes, and the intraocular pressure was increased to normal level in all eight eyes. CONCLUSION: Heterogeneous scleral transplantation has therapeutic effects in the treatment of hypotonic eyes after filtration surgery of glaucoma.

Adolescent↗

Locoregional/systemic chemotherapy of locally advanced/metastasized pancreatic cancer with a combination of mitomycin-C and gemcitabine and simultaneous follow-up by imaging methods and tumor markers.

Stimulated by surprising results in the first 7 patients treated with intraarterial/systemic chemotherapy with a combination of Mitomycin-C + Gemcitabine we now report on the data of 28 pancreatic cancer patients in comparison to 15 patients treated with gemcitabine alone(1000 mg/m2). Tumor response was evaluated on the basis of imaging methods, tumor markers and life quality parameters like body weight, pains and Karnofsky index etc. Tumor markers were monthly determined, imaging methods every 1-3 months. The locoregional/systemic approach included 3 week cycles with i.a. application of mitomycin-C + gemcitabine on day 1 and i.v. application of gemcitabine on days 8 and 15. The alltogether 125 cycles (mean 4 cycles per patient) resulted in 43% PR (n = 12), 1 CR (3%), 255 MR, 11% SD and 18% PD in the imaging methods and 20% CR, 60% PR, 4% MR and 12% SD in the course of the relevant tumor markers. Progression free survival amounted to a median of 7.5 (6) months defined by imaging methods (tumor markers). Second line treatments following new progress after effective locoregional approach with gemcitabine or a combination of gemcitabine + oxaliplatin did not result in a new tumor regression. However, third line therapy trials in 3 patients with high dose 5-FU or CPT 11 induced new antitumoral efficacy (survival of these tumors > 15, > 17 and > 28 months, n = 2 M1, n = 1 T3M0). About 75% of patients reported on a relevant benefit of life quality parameters. Side effects are on principle comparable to those of gemcitabine monotherapy, except for a tendency to a higher rate of pulmonary complications and 1 HUS observed. Even if not compared in a randomized study locoregional/systemic combined treatment modality seems to result in a higher rate of abjective tumor response defined by imaging methods as well as tumormarkers. Comparing tumor marker and imaging response to therapy CA 19-9 often showed a more rapid and subtle answer to therapy and an earlier new increase suggesting tumor markers as an essential part in the follow-up of these patients in order to optimize the patient's palliative treatment. Our results should stimulate the clinicians to rediscuss the chemosensitivity of exocrine pancreatic cancer and to perform prospective randomized studies focusing on combined gemcitabine approaches.

Aged↗

The effect of mitomycin C after long-term storage on human Tenon's fibroblast proliferation.

PURPOSE: To investigate the effect of mitomycin C (MMC) after long-term storage on proliferation of human Tenon's fibroblasts in vitro. METHODS: Human Tenon's fibroblasts in tissue culture were exposed for 5 minutes to MMC (0.4 mg/mL) that was either freshly prepared or had been stored for as long as 18 months at either 4 degrees C or -20 degrees C. The MTT colorimetric assay was used to determine the inhibition of proliferation as measured indirectly by mitochondrial activity. RESULTS: The inhibition rate was 88% using fresh MMC, and declined to a mean of 73% when using MMC that had been stored for as long as 18 months at 4 degrees C; this decrease was not statistically significant. The mean inhibition for MMC stored at -20 degrees C was 68%, and this was significantly less than inhibition with fresh MMC. Inhibition did not vary significantly with MMC after different storage times. CONCLUSION: Mitomycin C continues to have strong in vitro antiproliferative effects when stored for as long as 18 months at 4 degrees C or -20 degrees C. A significant decline in potency compared with fresh MMC occurs when MMC is stored at -20 degrees C.

Cell Division↗

[A preliminary report of antiscar formation effect by subconjunctival injection of mitomycin C before trabeculectomy in glaucoma].

To improve the function of filtering blebs and increase the successful rate of the trabeculectomy, mitomycin C injection 0.02 mg.ml-1 was given subconjunctivally at the operative site before trabeculectomy in 32 patients (38 eyes) with moderate or late glaucoma. All patients were followed up for 6 to 12 months. The results showed that the rate of functional blebs were 93.7%. The successful rate of the operation was 94.7%. The common postoperative complication was shallow anterior chamber (7.9%). These findings indicate that the subconjunctival injection of mitomycin C before operation is a safe, effective method for antiscar formation.

Adult↗

Intraoperative use of mitomycin C in the treatment of recurrent pterygium.

The prevalence rate of pterygium in Papua New Guinea (PNG) is as high as 15%. Recurrence rates up to 50% are encountered after primary excision. In a country such as PNG where resources in terms of funds and manpower are limited, a simple procedure had to be identified to reduce this alarmingly high rate of pterygium recurrence. This article compares the results of a randomized masked study involving the single intraoperative application of 0.02% mitomycin C solution in 65 eyes undergoing surgery for recurrent pterygium using the bare sclera technique with a similar group of 65 patients in which the drug was not used. The results indicate that a single intraoperative application of mitomycin C solution was enough to reduce the recurrence rate of pterygium to 3% in the treated group as compared to 48% in the untreated group at the end of a 12-month follow-up. In the study it was also seen that, in PNG, pterygia were more common in females and that recurrences tended to occur early and were obvious in the first few weeks following surgery.

Adult↗

Clinical results of Ahmed glaucoma valve implantation in refractory glaucoma with adjunctive mitomycin C.

OBJECTIVE: To study the surgical outcome and complications of Ahmed glaucoma valve (AGV) implantation with mitomycin C (MMC) in refractory glaucoma. PATIENTS AND METHODS: The authors retrospectively reviewed the records of 40 eyes in 37 consecutive patients who underwent combined AGV with MMC (0.4 mg/mL; 5 minutes). All patients had a minimum of 6 months of follow-up. Outcome measures were best corrected visual acuity, intraocular pressure (IOP), the number of medications, success rates, and the incidence of complications. RESULTS: The Kaplan-Meier life table analysis revealed that the probabilities of surgical success based on our success criteria at 1 year and 2 years postoperatively were 80% and 77%, respectively. Postoperative IOP was significantly lower at all follow-up intervals. At the final visit fewer glaucoma medications were used (2.5 vs 0.7, preoperative vs postoperative). The most frequent complication was hypotony (17%). CONCLUSION: In this retrospective case series with relatively short follow-ups, AGV implantation with mitomycin C in refractory glaucoma appears to be effective without increased complication rates.

Adolescent↗

[The effect of combination chemotherapy to adapted to chronotherapy with 5-fluorouracil, leucovorin, mitomycin C and cisplatin in patients with gastric or colorectal cancer].

We performed combination chemotherapy adapted to chronotherapy with 5-fluorouracil, leucovorin, mitomycin C and cisplatin in 11 patients with gastric cancer and 7 with colorectal cancer. Treatment consisted of a 5-day course of continuous arterial or intravenous infusion of 5-FU (500 mg/body/day), arterial or intravenous infusion of leucovorin (20 mg/body/day) at 6:00 p.m. on days 1-5, arterial or intravenous infusion of mitomycin C (2 mg/body) at 9:00 a. m. on day 5, and arterial or intravenous infusion of cisplatin (20-80 mg/body) at 6:00 p.m. on day 5. The effective rate against gastric cancer was 73%; however, the effective rate against colorectal cancer was 29%. During and after this therapy, there was only a little appetite loss, nausea and stomatitis.

Aged↗

[Mitomycin C in open angle glaucoma surgery with previous failed glaucoma surgery].

PURPOSE: This study investigates the results of trabeculectomy with peroperative topical application of mitomycin-C performed on eyes with previous failed glaucoma filtering surgery. METHODS: The study includes 34 eyes of 26 patients operated on open angle glaucoma between March 1992 and October 1996, with a minimum of 6 months follow-up (mean 28.1 months). All the eyes had undergone prior one (27) o two (7) filtering surgeries. We evaluated intraocular pressure (IOP) and treatment reduction after surgery. Success was defined as IOP <20 mmHg, without deterioration of the visual field and/or papilla and without oral carbonic anhydrase inhibitors (OCAI) treatment. RESULTS: Average IOP decrease (p<0,001) from 21.06+/-3.70 mmHg to 13.88+/-2.42 mmHg after surgery and the number of medications dropped from 2.44+/-0.69 to 0.68+/-1.02 (p<0.01). The success rate was 88.2%. The major complication was hypotony maculopathy in 3 eyes (8.8%). CONCLUSIONS: Trabeculectomy with mitomycin-C decreases IOP and postoperative medications in eyes with previous unsuccessful filtering surgery.

Adult↗

Mitoxantrone, mitomycin-C, methotrexate combination chemotherapy with radiotherapy and/or surgery in stage III (T4B, NO-2, M0) breast cancer.

Results of primary surgery with or without locoregional radiotherapy (LRRT) are poor in stage III (T4b, NO-2, M0) breast cancer. Combination of mitoxantrone, mitomycin-c and methotrexate (MMM) has been reported to be as efficacious as doxorubicin based protocols with advantages of reduced nausea, vomiting, alopecia and cardiotoxicity. We tested MMM chemotherapy with LRRT and surgery in locally advanced breast cancer (LABC) with a view to assess response, survival, breast conservation, cost and toxicity. Fifty two previously untreated patients were given Mitoxantrone: 8 mg/m sq by infusion on days 1 and 21, Mitomycin-C: 8 mg/m sq by infusion on day 1 and Methotrexate: 35 mg/m sq i.v. on days 1 and 21. Cycles were repeated every 42 days. After 3 cycles LRRT was given if lump reduced to less than 2 cms. Otherwise patients were subjected to modified radical mastectomy (MRM) or radical mastectomy (RM). Following this 3 more cycles of chemotherapy were given. Patients with soft tissue, skin or heavy nodal involvement also received LRRT. Tamoxifen 20 mg daily was prescribed at the end of chemotherapy to postmenopausal patients. Complete/partial responses were seen in 5 and 26 patients, respectively after chemotherapy giving an overall response of 59.5%. Twenty four patients each had LRRT and MRM/RM. Responses could be significantly enhanced by LRRT/and or surgery. Nineteen out of 25 relapses were at distant sites. Breast conservation was achieved in 24/52 (46%) patients. Three year disease free and overall survival was 54% and 65%, respectively. There was 1 toxic death. Severe prolonged myelosuppresion was seen in those who also received LRRT. Mucositis, alopecia, nausea and vomiting were minor problems. Overall, combination was less expensive than doxorubicin based protocols.

Adult↗

Homology-directed dna repair, mitomycin-c resistance, and chromosome stability is restored with correction of a Brca1 mutation.

Chromosomal breaks occur spontaneously as a result of normal DNA metabolism and after exposure to DNA-damaging agents. A major pathway involved in chromosomal double-strand break repair is homologous recombination. In this pathway, a DNA sequence with similarity to a damaged chromosome directs the repair of the damage. The protein products of the hereditary breast cancer susceptibility genes, BRCA1 and BRCA2, interact with the Rad51 protein, a central component of homologous repair pathways. We have recently shown that this interaction is significant by demonstrating that Brca1- and BRCA2-deficient cells are defective in homology-directed chromosomal break repair. We confirm that Brca1-deficient embryonic stem (ES) cells are defective in gene targeting and homology-directed repair of an I-Sce I-induced chromosome break. The phenotypic paradigm that defines homology-directed repair mutants is extended to these Brca1-deficient cells by the demonstration of 100-fold sensitivity to the interstrand cross-linking agent mitomycin-C and spontaneous chromosome instability. Interestingly, although chromosome aberrations were evident, aneuploidy was not observed. Repair phenotypes are partially restored by expression of a Brca1 transgene, whereas correction of one mutated Brca1 allele through gene targeting fully restores mitomycin-C resistance and chromosome stability. We conclude that the inability to properly repair strand breaks by homology-directed repair gives rise to defects in chromosome maintenance that promote genetic instability and, it is likely, tumorigenesis.

Animals↗

Phase II study of hexamethylmelamine alone and in combination with mitomycin C and vincristine in advanced breast carcinoma.

Fifty-three patients with metastatic breast carcinoma were randomized to treatment with hexamethylmelamine (HMM) as a single agent versus a three-drug reimen of HMM, vincristine, and mitomycin C (HOM). All patients had received prior treatment with 5-fluorouracil, Adriamycin, and cyclophosphamide with or without methotrexate. HMM alone was used in a dose of 300 mg/m2/day x 14 days every 21 days. In the HOM regimen, the HMM dose was 200 mg/m2/day x 21 days, the vincristine dose was 1.5 mg on Days 1, 8, and 15, and the mitomycin C dose was 12 mg/m2 once every 6 weeks. No objective responses were observed with HMM in 15 evaluable patients. The HOM regimen resulted in five partial responses among the 27 evaluable patients. Gastrointestinal toxicity was the limiting toxicity of HMM, and thrombocytopenia was the major toxicity of the HOM regimen.

Adult↗