SEARCH · PubMed Health

Results for “Pathologic response”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 595 records · Page 33Linked to original sources

PubMed1994

Proliferating cell nuclear antigen and mitotic activity in rectal cancer: predictor of response to preoperative irradiation.

PURPOSE: This study examines the association between the pathologic response of rectal cancer after irradiation and its pretreatment proliferative state as assayed by proliferating cell nuclear antigen (PCNA) and mitotic activity. PATIENTS AND METHODS: Ninety patients with clinical stage T3 and T4 rectal cancer received preoperative irradiation followed by surgery. Pretreatment tumor biopsies were scored for PCNA activity (number of tumor cells staining immunohistochemically with an anti-PCNA monoclonal antibody) and the number of mitoses per 10 high-powered fields (hpf). Postirradiation surgical specimens were examined for extent of residual disease. RESULTS: The tumors of 33 of 90 patients (37%) exhibited marked pathologic downstaging (no residual tumor or cancer confined to the rectal wall) after preoperative irradiation. Two features were independently associated with the likelihood of marked pathologic regression after preoperative irradiation: lesion size and PCNA/mitotic activity. When stratified by tumor size, marked tumor regression occurred most frequently in smaller tumors with high PCNA/mitotic activity compared with larger tumors with lower PCNA/mitotic activity. Intermediate downstaging rates were seen for small or large tumors with moderate PCNA/mitotic activity. CONCLUSION: Tumor PCNA/mitotic activity predicts the likelihood of response to irradiation, which may aid in formulating treatment policies for patients with rectal cancer.

Adult↗

PubMed1985

HAC-Cytoxan (cyclophosphamide) chemotherapy for ovarian carcinoma. Alternating chemotherapy with intensification.

Twenty-two previously untreated patients with adenocarcinoma of the ovary were treated with 28 day cycles of hexamethylmelamine, Adriamycin (doxorubicin), and cisplatin (HAC) for 9 months followed by three monthly cycles of intense intravenous cyclophosphamide. An overall response frequency of 82% (18/22) was achieved. Complete pathologic responses (CPR) documented by second look operations were found in 50% (11/22); however, patients considered to be free of disease (prolonged complete clinical response refusing "second look" and CPR) totaled 59%. Median survival has not been reached after a median follow-up of 34 months. No major or life threatening toxicity was encountered. HAC followed by cyclophosphamide is a highly effective regimen that may be easily administered on an outpatient basis with comparatively little toxicity.

Adenocarcinoma↗

PubMed2007

Detection of interval distant metastases: clinical utility of integrated CT-PET imaging in patients with esophageal carcinoma after neoadjuvant therapy.

BACKGROUND: The objective of the study was to determine the utility of integrated computed tomography / positron emission tomography (CT-PET) imaging for detecting interval distant metastases and assessing therapeutic response in patients with locally advanced, potentially resectable esophageal carcinoma after neoadjuvant therapy. METHODS: A retrospective study was performed of 88 patients with potentially resectable esophageal carcinoma who received neoadjuvant therapy before planned surgical resection. CT-PET before and after completion of neoadjuvant was used for evaluating therapeutic response; response criteria were based on qualitative and semiquantitative analyses. RESULTS: Neoadjuvant therapy comprised chemoradiotherapy in 85 patients, with prior induction chemotherapy in 39 patients. Fifty-five patients proceeded to esophagectomy. Repeat CT-PET was performed after induction chemotherapy (n = 23) and after completing chemoradiotherapy (n = 85). CT-PET identified the interval appearance of metastatic disease in 7 (8%) patients. For assessment of locoregional therapeutic response, CT-PET was unable to predict pathological response to neoadjuvant therapy in the primary tumor or locoregional lymph nodes. CT-PET had sensitivity, specificity, and positive and negative predictive values of 57%, 46%, 39%, and 64%, respectively, for detection of residual macroscopic malignancy within the primary tumor; and sensitivity, specificity, and positive and negative predictive values of 0%, 90%, 0%, and 69% for detection of residual malignancy within resected lymph nodes. CONCLUSIONS: CT-PET performed after neoadjuvant therapy in patients with potentially resectable esophageal carcinoma is important for detecting interval metastases that preclude surgical resection, but is of limited utility for assessing locoregional therapeutic response.

Adenocarcinoma↗

PubMed2005

Clinical response to neoadjuvant docetaxel predicts improved outcome in patients with large locally advanced breast cancers.

PURPOSE: In the adjuvant setting, taxanes modestly improve clinical outcome and survival. The goal of the present study was to define the efficacy of neoadjuvant docetaxel in treatment-naïve large, locally advanced breast cancers and to better understand docetaxel's mechanism of action by evaluating biomarker modulation in response to treatment. PATIENTS AND METHODS: Fifty-one patients were enrolled. Patients received four cycles of docetaxel (100 mg/m2 q3weeks) followed by surgery and four cycles of doxorubicin and cyclophosphamide (60/600 mg/m2 q3weeks). Radiation and hormonal therapy were given if clinically indicated. Clinical responses were assessed at completion of neoadjuvant docetaxel. Pathological responses were considered complete (pCR) if no tumor cells were identified in the surgical specimen or near complete (npCR) if only occasional scattered tumor cells were seen. Proliferation (Ki-67) and apoptosis (cleaved caspase-3) were measured by IHC in tissue obtained at baseline and at surgery. RESULTS: The median tumor size was 9 cm (range 4-30 cm). Objective response rate was 75% with clinical complete response in 27%, partial response in 48%, and stable disease in 25% of the patients. pCR/npCR was reported in 20% of patients. With a median follow up of 28 months, 98 and 78% of the patients were alive at 12 and 24 months, respectively. Overall survival at 24 months was significantly better in patients who achieved a clinical response, 85 versus 51%, p = 0.008, but pCR/npCR was not a significant predictor of outcome. Apoptosis was induced in clinical responders (p = 0.002), while the proliferation index did not change significantly. In patients who had no clinical response to docetaxel, neither apoptosis nor proliferation changed significantly. CONCLUSION: Neoadjuvant single agent docetaxel is effective in treating patients with large locally advanced breast cancer and clinical response is associated with improved survival. Docetaxel acts therapeutically by inducing apoptosis and this can be used as a marker of response.

Adult↗

PubMed1997

Preoperative chemotherapy versus surgical therapy alone for squamous cell carcinoma of the esophagus: a prospective randomized trial.

OBJECTIVE: This study investigated the role of preoperative chemotherapy in squamous cell cancer of the esophagus. METHODS: A prospective randomized trial was undertaken in 147 patients: 74 received preoperative chemotherapy comprising cisplatin and 5-fluorouracil and 73 had surgical therapy alone. End points were cancer and therapy-related deaths. RESULTS: Sixty-six patients (89%) in the chemotherapy group underwent resection compared with 69 (95%) in the control group (p = not significant). Of the 60 patients who had resection after completing the chemotherapy program, 35 (58%) had a significant response, of whom four (6.7%) had a complete pathologic response. Postoperative mortality rates were 8.3% and 8.7% in the chemotherapy and control groups, respectively (p = not significant). Significant downstaging was evident with chemotherapy; curative resections were possible in 67% of these patients compared with 35% in the control group (p = 0.0003). T3 and T4 tumors were found in 67% and 91% of the chemotherapy and control groups, respectively (p = 0.0002). The respective figures for N1 disease were 70% and 88% (p = 0.009). An intent-to-treat analysis of survival showed no significant difference between the two groups. Median survivals were 16.8 and 13 months, respectively (p = 0.17). Of those who completed the chemotherapy and resection, responders fared better than control patients. Median survivals were 42.2 months and 13.8 months, respectively (p = 0.003). Median survival (8.3 months) was worse for nonresponders than for control patients (p = 0.03). The recurrence pattern suggested a significant reduction in locoregional disease with chemotherapy. CONCLUSIONS: Preoperative chemotherapy was safe and resulted in significant downstaging and an increased likelihood of curative resection. Survival was not better than that in the surgery-alone group, but responders did fare better than nonresponders.

Aged↗

PubMed2001

Implications of molecular contacts and signaling initiated by Neisseria gonorrhoeae.

Neisseria gonorrhoeae employs diverse strategies with which to adhere to and invade host cells during the course of infection. These primary encounters provide means by which biologically active molecules can be efficiently targeted to disrupt or exploit normal host cell metabolism and immune response elements, which in turn leads to the pathological responses characteristic of gonococcal disease. Current studies have begun to elucidate in detail the molecular interactions orchestrating these processes and the signaling events that they provoke.

Animals↗

PubMed2003

Neoadjuvant docetaxel in locally advanced breast cancer.

Neoadjuvant chemotherapy produces substantial increases in clinical response rates and rates of breast conserving therapy. Pathologic response rate, though generally low, is an important outcome as it is presumably associated with eradication of micrometastatic disease and may likely result in improved outcomes. Anthracyclines have long been considered the most efficacious chemotherapy agents for neoadjuvant therapy of early breast cancer. Unfortunately, not all patients respond to neoadjuvant anthracycline-based chemotherapy. In an effort to improve primary tumor response, docetaxel, an active agent in breast cancer, has been evaluated in the neoadjuvant setting. Several randomized trials, including the NSABP B-27, GEPAR-duo, and the Aberdeen trial, evaluating docetaxel in sequence with a doxorubicin-based neoadjuvant regimen have been reported, with encouraging findings. We designed the Aberdeen trial with two primary aims: (1) to evaluate primary docetaxel in patients that initially fail a neoadjuvant anthracycline-based polychemotherapy regimen, and (2) to compare a docetaxel-based neoadjuvant regimen with a standard anthracycline-based regimen in patients who do respond to the first four cycles of the anthracycline-based regimen. Eligible patients (n = 162) had previously untreated large (> or = 3 cm) or locally advanced (T3, T4, T x N2) breast cancer. All received four cycles of CVAP, after which clinical response was assessed. Responding patients were then randomized to four additional cycles of CVAP or to docetaxel 100 mg/m2 every 3 weeks for four cycles. Patients failing to respond to CVAP received the docetaxel regimen. After the first four cycles of CVAP, the overall response rate (ORR) was 67%. Ultimately, responses were higher in the group randomized to docetaxel compared with those continuing CVAP (cCR: 94% vs. 66%; p = 0.001; pCR 34% vs. 16%; p = 0.04). The addition of docetaxel improved overall survival and disease-free survival for patients responding to four cycles of CVAP as compared with those receiving eight cycles of CVAP. Relative dose intensity was higher and the incidence of severe leukopenia was lower in the group randomized to docetaxel. These data and data from the NSABP B-27 and GEPAR-duo trials strongly support a combined anthracycline/docetaxel regimen in the neoadjuvant setting.

Antineoplastic Agents, Phytogenic↗

PubMed2004

High curative resection rate with weekly cisplatin, 5-fluorouracil, epidoxorubicin, 6S-leucovorin, glutathione, and filgastrim in patients with locally advanced, unresectable gastric cancer: a report from the Italian Group for the Study of Digestive Tract Cancer (GISCAD).

The aim of the present study was to evaluate the role of a weekly preoperative chemotherapy in locally advanced, unresectable gastric cancer. In all, 82 patients with an Eastern Oncology Cooperative Group PS <or=2 and normal cardiac function were enrolled onto the study. Surgical unresectability was confirmed in 52 patients (63%) at laparotomy, and in 30 (27%) cases by CT scan of the abdomen and endoscopic ultrasonography. Chemotherapy treatment was: cisplatin 40 mg x m(-2); 5-fluorouracil 500 mg x m(-2); epidoxorubicin 35 mg x m(-2); 6S-leucovorin 250 mg x m(-2) and glutathione 1.5 g x m(-2) (PELF). One cycle consisted of 8 weekly treatments. Response to chemotherapy was observed in 40 of 82 patients (49%): six (7%) complete and 34 (41%) partial responses, and in four (5%) cases a complete pathological response was confirmed. Of the 40 responding patients, 37 (45%) had potentially curative surgery. Grade 3/4 leucopenia and thrombocytopenia occurred in three and two patients. At a median follow-up of 48 months, 25 of the 37 resected patients (68%) were alive and 24 (65%) were disease free. The median and 4-year survival for the whole group was 17 months and 31%, respectively. The median survival was 12 months for inoperable patients and it was not reached in resected patients.

Adult↗

PubMed2003

Correlation of p53 status with outcome of neoadjuvant chemotherapy using paclitaxel and doxorubicin in stage IIIB breast cancer.

BACKGROUND: The role of p53 in modulating apoptosis has suggested that it may affect efficacy of anticancer agents. We prospectively evaluated p53 alterations in 73 patients with locally advanced breast cancer (IIIB) submitted to neoadjuvant chemotherapy. PATIENTS AND METHODS: Patients received three cycles of paclitaxel (175 mg/m2) and doxorubicin (60 mg/m2) every 21 days. Tumor sections were analyzed before treatment for altered patterns of p53 expression using immunohistochemistry and DNA sequencing. RESULTS: An overall response rate of 83.5% was obtained, including 15.1% complete pathological responses. The regimen was well tolerated with 17.7% grade 2/3 nausea and 12.8% grade 3/4 leukopenia. There was a statistically significant correlation between response and expression of p53. Of the 25 patients who obtained a complete clinical response, two were classified as positive (P = 0.004, chi-square). Of 11 patients who obtained a complete pathological remission, one was positive (P = 0.099, chi-square). Discussion The combination is highly effective in locally advanced breast cancer. A negative expression of p53 indicates a higher chance of responding to this regimen. The p53 status may be used as a biological marker to identify those patients who would benefit from more aggressive treatments.

Adult↗

PubMed2003

[Docetaxel in neoadjuvant therapy of early-stage non-small cell carcinoma].

The combination of docetaxel and cisplatin is one of the standard chemotherapy regimens which has been shown to improve survival and quality of life in patients with advanced non-small cell lung cancer (NSCLC). Docetaxel has therefore been administered by several groups in the neoadjuvant setting in stage-III disease. In combination with cisplatin, the response rate, the complete resection rate and the pathological response rate were similar as in other regimens, postoperative morbidity and mortality, however, seemed reduced when compared with combinations including mitomycin C. Furthermore, there was an association of the chemotherapy activity in mediastinal lymph nodes of patients with a NSCLC (stage IIIA) and overall survival. Based on these results, the cytostatic combination of docetaxel/cisplatin has been chosen for further use in large randomized studies.

Antineoplastic Agents, Phytogenic↗

PubMed1991

Chemotherapy (CAP) for the treatment of advanced ovarian cancer and second-effort surgery in the second look.

Seventy-two patients with advanced ovarian cancer received CAP chemotherapy followed by laparotomy and 'second-effort' surgery. The overall response to CAP therapy was 80%. A complete pathological response (CPR) was obtained in 16 patients and partial microscopic (PMiR) and macroscopic responses in 7 and 33 cases, respectively. The actuarial survival for the entire group was 36% at 50 months with a median survival of 34 months. No significant differences in survival between the CPR and PMiR groups were found. Radical second-effort surgery showed a somewhat beneficial effect. The tumor size before chemotherapy (less than 5 cm) and FIGO stage III had a significantly favorable effect on response rate and survival.

Adult↗

PubMed2001

Expression of LRP and MDR1 in locally advanced breast cancer predicts axillary node invasion at the time of rescue mastectomy after induction chemotherapy.

BACKGROUND: Axillary node status after induction chemotherapy for locally advanced breast cancer has been shown on multivariate analysis to be an independent predictor of relapse. However, it has been postulated that responders to induction chemotherapy with a clinically negative axilla could be spared the burden of lymphadenectomy, because most of them will not show histological nodal invasion. P-glycoprotein expression in the rescue mastectomy specimen has finally been identified as a significant predictor of patient survival. MATERIALS AND METHODS: We studied the expression of the genes encoding multidrug resistance associated protein (MDR1) and lung cancer associated resistance protein (LRP) in formalin-fixed, paraffin-embedded tumor samples from 52 patients treated for locally advanced breast cancer by means of induction chemotherapy followed by rescue mastectomy. P-glycoprotein expression was assessed by means of immunohistochemistry before treatment in 23 cases, and by means of reverse-transcriptase-mediated polymerase chain reaction (RT-PCR) after treatment in 46 (6 failed). LRP expression was detected by means of immunohistochemistry, with the LRP-56 monoclonal antibody, in 31 cases before treatment. Immunohistochemistry for detecting the expression of c-erb-B2, p53, Ki67, estrogen receptor and progesterone receptor are routinely performed in our laboratory in every case, and the results obtained were included in the study. All patients had received between two and six cycles of standard 5-fluorouracil, doxorubicin and cyclophosphamide (FAC) chemotherapy, with two exceptions [one patient received four cycles of a docetaxel-adriamycin combination, and the other four cycles of standard cyclophosphamide-methotrexate-5-fluorouracil (CMF) polychemotherapy]. Response was assessed in accordance with the Response Evaluation Criteria In Solid Tumors (RECIST). By these, 2 patients achieved a complete clinical response, 37 a partial response, and the remaining 13 showed stable disease. This makes a total clinical response rate of 75.0%. None achieved a complete pathological response. RESULTS: MDR1 mRNA expression detected by RT-PCR was associated with the presence of invaded axillary nodes at surgery in 18/22 cases (81.8%), compared with 13/24 (54.2%) in the group with undetectable MDR1 expression. This difference was statistically significant (P < 0.05). LRP expression in more than 20% of tumor cells before any treatment was associated with axillary nodal metastasis after chemotherapy and rescue mastectomy in 17/23 cases, compared with 3/8 in nonexpressors. Again, this difference was highly significant (P < 0.01). LRP expression before treatment and MDR1 mRNA expression after treatment were significantly interrelated (P < 0.001), which might reflect the presence of chemoresistant clones liable to metastasize to the regional nodes. Persistence of previously detected MDR1-positivity after treatment (7/9 compared with 0/2 cases) was significantly associated with axillary node metastasis (P < 0.05). Finally, in a logistic regression multivariate model, histology other than ductal, a Ki67 labeling index of at least 20% and the combination of LRP and MDR1 positivity emerged as independent predictors of axillary node invasion at the time of rescue mastectomy. CONCLUSION: The expression of different genes involved in resistance to chemotherapy, both before and after treatment with neoadjuvant, is associated with the presence of axillary node invasion at rescue surgery in locally advanced breast cancer. This might reflect the presence of intrinsically resistant clones before any form of therapy, which persist after it, and could be helpful both for prognosis and for the choice of individual treatment.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1993

Metabolic monitoring of breast cancer chemohormonotherapy using positron emission tomography: initial evaluation.

PURPOSE: We assessed the feasibility of noninvasive metabolic monitoring of cancer chemohormonotherapy using sequential quantitative positron emission tomographic (PET) scans of tumor glucose metabolism with the glucose analog 2-[18F]-fluoro-2-deoxy-D-glucose (FDG). PATIENTS AND METHODS: Eleven women with newly diagnosed primary breast cancers larger than 3 cm in diameter beginning a chemohormonotherapy program underwent a baseline and four follow-up quantitative PET scans during the first three cycles of treatment (days 0 to 63). Tumor response was sequentially determined clinically, radiographically, and then pathologically after nine treatment cycles. RESULTS: Eight patients had partial or complete pathologic responses. Their maximal tumor uptake of FDG assessed by PET decreased promptly with treatment to the following: day 8, 78 +/- 9.2% (P < .03); day 21, 68.1 +/- 7.5% (P < .025); day 42, 60 +/- 5.1% (P < .001); day 63, 52.4 +/- 4.4% (P < .0001) of the basal values. Tumor diameter did not decrease significantly during this period through 63 days. Prompt decreases in the FDG influx rate (K) from basal levels (from .019 to .014 mL/cm3/min) after 8 days of treatment (P < .02) and in the estimated rate of FDG phosphorylation to FDG-6-phosphate (k3) from .055 to .038 min-1 after 8 days of treatment (P < .02) to .029 +/- .004 min-1 at 21 days) (P < .02) were observed. Three nonresponding patients had no significant decrease in tumor uptake of FDG (81 +/- 18% of basal value), influx rate (.015 to .012 mL/cm3/min), or tumor size (81 +/- 12% of basal diameter) comparing basal versus 63-day posttreatment values. CONCLUSION: Quantitative FDG PET scans of primary breast cancers showed a rapid and significant decrease in tumor glucose metabolism after effective treatment was initiated, with the reduction in metabolism antedating any decrement in tumor size. No significant decrease in FDG uptake (SUV) after three cycles of treatment was observed in the nonresponding patients. FDG PET scanning has substantial promise as an early noninvasive metabolic marker of the efficacy of cancer treatment.

Adult↗

PubMed1993

Clinical activity of a cytotoxic fusion protein in the treatment of cutaneous T-cell lymphoma.

PURPOSE: A phase I trial in patients with refractory hematologic malignancies was performed at our institution to test the clinical relevance of the selective cytotoxic activity of the interleukin-2 (IL-2)-diphtheria toxin fusion protein, DAB486IL-2. A subset of five patients from this trial, all with cutaneous T-cell lymphomas (CTCL), forms the basis of this report. PATIENTS AND METHODS: Two treatment schedules were used. One patient received DAB486IL-2 at a dose of 0.075 mg/kg/d intravenous (i.v.) bolus over 15 minutes daily for 5 consecutive days. The other four patients received DAB486IL-2 at a dose of 0.1 mg/kg as an i.v. infusion over 180 minutes weekly for 5 consecutive weeks. RESULTS: Three of the five CTCL patients achieved significant tumor responses. One patient attained a complete clinical and pathologic response (CR), which has been sustained without any interval treatment for 33+ months. Two other patients achieved partial responses (PRs) of 17+ and 4 months' duration, respectively. Treatment was well tolerated. The most common adverse effect was a transient increase in hepatic transaminases experienced by all five patients. CONCLUSION: The growth factor-cytotoxin fusion protein DAB486IL-2 demonstrated significant clinical activity with acceptable toxicity in a group of heavily pretreated patients with CTCL.

Diphtheria Toxin↗

PubMedDate not supplied

Experimental pneumonia in red deer (Cervus elaphus L) produced by an ovine chlamydia.

An isolate of Chlamydia psittaci from ovine pneumonia produced extensive pneumonia in red deer after endobronchial inoculation. Associated clinical signs lasting for several days included pyrexia, inappetance, increased pulse and respiration rate, and physical distress after handling, but no coughing or upper respiratory symptoms. Histologically, an acute exudative reaction was present after two days, and an early proliferative response after seven days. Both the clinical and pathological responses were more marked than those usually associated with chlamydial pneumonia in other large animals after endobronchial infection. A small survey for chlamydial antibody in wild red deer was negative.

Animals↗

PubMed1992

Intra-arterial induction chemotherapy for soft tissue sarcomas.

One hundred-one patients were treated in our institution with intra-arterial preoperative adriamycin (i.a. ADR) for large soft tissue sarcomas of the extremities, 45% recurrent at entry. Of the 78 high grade evaluable patients 38% had clinical and 45% had pathological responses to chemotherapy. Limb conservative surgery was performed in 80% of cases, with about 10% improvement made possible by the preoperative treatment. The local recurrence rate was 29%, and 50% five-year actuarial survival with a median follow-up of 68 months. These poor results are related to the severe selection of high risk cases. The clinical parameter of response was highly predictive of survival: 63% versus 36% (p = 0.01) 5-year survival in the group of responders and non-responders, respectively, whereas the pathological parameter of response was not so predictive. The improved effect of delivering the drug intra-arterially is theoretically expected but not proved in our experience. The major practical effect of this induction chemotherapy is the selection of patients with better prognosis and the possibility of perform, in some cases, easier limb salvage procedures. The last regimen combining i.a. ADR + i.v. Ifosfamide seems to provide little better but not yet significant results.

Adolescent↗

PubMed1977

Methylphenidate hydrochloride effects on psychological tests in acute schizophrenic and nonpsychotic patients.

Actively psychotic schizophrenic and nonpsychotic psychiatric inpatients received intravenous methylphenidate hydrochlroide (0.5 mg/kg). Each patient was rated for level of psychosis and talkativeness, and each received the Holtzman projective ink blot tests and the Kent-Rosanoff word-association tests before, during, and after methylphenidate infusion. Minnesota Multiphasic Personality Inventory Goldberg Index scores were also obtained as a general measure of psychosis. For the entire patient group, methylphenidate infusion was followed by a significant increase in talkativeness and psychosis ratings and in pathological responses to the Holtzman ink blot test. There was a significant decrease in common word associations. Since neither of the psychological tests allow more than one response per item, it appears that methylphenidate truly effects pathological thought processes and decreases common word associations as such, rather than merely making these processes more evident by increasing verbalization.

Acute Disease↗

PubMed1983

Preoperative chemotherapy and radiation therapy in the management of anal epidermoid carcinoma.

Management of epidermoid carcinoma of the anus has been primarily surgical in the past. Since it is a relatively rare entity, meaningful survival statistics are difficult to obtain. Five-year survival rates fall between 35 and 68% in patients treated with surgery and/or radiotherapy. Based on preliminary studies indicating promising results with the use of mitomycin C and 5-fluorouracil (5-FU) chemotherapy combined preoperatively with radiation therapy, these authors initiated a protocol in 1973 utilizing this multimodality approach. The preoperative treatment consisted of mitomycin C 15 mg/m2 IV bolus on day 1 and 5-FU 750 mg/m2/24 hours continuous infusion for five days. Radiation followed chemotherapy and consisted of 3000 rad given at 200 rad per day for 15 fractions. Of 37 patients entered on the protocol, 30 had primary disease and seven had been previously treated and had local recurrences. Median follow-up has been 28 months (range, 5-74 months). Of 31 patients with measurable lesions, 29 (94%) had major clinical responses (CR + PR) to the combined chemotherapy and radiation. Pathologic responses were also impressive with 53% (17/32) showing no evidence of residual tumor in the subsequently resected surgical specimen. Of the 37 patients treated, seven (19%) have had recurrences. The recurrence rate was 4/17 (24%) for those who had local excision following complete response to therapy as opposed to 3/18 (17%) for those treated by abdominoperineal resection. Thus it appears that the combination of preoperative mitomycin C and 5-FU with radiotherapy is effective at least in significantly downstaging this uncommon malignancy. Its ultimate effect on recurrence rate and overall patient survival awaits longer follow-up.

Adult↗