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R Komaki

Publications and source records attributed to R Komaki.

At least 73 records · Page 4Linked to original sources

Induction cisplatin/vinblastine and irradiation vs. irradiation in unresectable squamous cell lung cancer: failure patterns by cell type in RTOG 88-08/ECOG 4588. Radiation Therapy Oncology Group. Eastern Cooperative Oncology Group.

PURPOSE: To analyze disease failure patterns by pretreatment characteristics and treatment groups in a prospective randomized trial. METHODS AND MATERIALS: Patients with medically inoperable Stage II, unresectable IIIA and IIIB nonsmall cell lung cancer with KPS > or =70 and weight loss < or =5% were randomized to one of three treatment groups: standard radiation therapy with 60 Gy at 2.0 Gy per day (STD RT), induction chemotherapy with cisplatin 100 mg/m2 days 1 and 29 with vinblastine 5 mg/m2 weekly for 5 weeks followed by 60 Gy at 2.0 Gy per day (CT + RT), or hyperfractionated radiation therapy with 69.6 Gy at 1.2 Gy b.i.d. (HFX RT). Of 490 patients enrolled, 458 were evaluable. Minimum and median periods of observation for this analysis were 4 years and 6 years, respectively. RESULTS: Pretreatment characteristics were equally distributed. Toxicities were previously reported. Median survival rates were 11.4, 13.6, and 12.3 months for STD RT, CT + RT, and HFX RT, respectively (log rank p = 0.05, Wilcoxon p = 0.04). Survivals were 20, 31, and 24% at 2 years, and 4, 11, and 9% at 4 years in the STD RT, CT + RT, and HFX RT groups, respectively. There were no differences in local tumor control rates among the treatments. Patterns of first failure showed less distant metastasis (DM) (other than brain) for CT + RT compared to the RT alone arms (p = 0.04). Within squamous cell carcinoma (SCC), DM (other than brain) rates were 43%, 16%, and 38% in SCC for STD RT, CT + RT, and HFX RT, respectively (p = 0.0015). Patients with peripheral/chest wall lesions were significantly more likely to fail first in the thorax when treated on STD RT compared to CT + RT and HFX RT (p = 0.009). Survival rates were similar among the treatment arms for patients with squamous cell carcinoma. Among patients with nonsquamous cell carcinoma, failure patterns did not differ by treatment group, but survival was significantly better in those who were treated by induction chemotherapy (p = 0.04). CONCLUSION: Patients with squamous cell carcinoma treated on the CT + RT arm had a significant reduction of first DM other than brain, but there was difference in survival. Survival favored CT + RT in nonsquamous carcinoma despite similar failure patterns. Reasons for improved survival with CT + RT in NSCLC are not yet available.

Adenocarcinoma↗

Randomized study of chemotherapy/radiation therapy combinations for favorable patients with locally advanced inoperable nonsmall cell lung cancer: Radiation Therapy Oncology Group (RTOG) 92-04.

PURPOSE: The purpose of this study was to compare the severity and distribution of the toxicities associated with the two different combinations of chemotherapy and radiotherapy. METHODS AND MATERIALS: This prospective randomized trial studied toxicities associated with induction chemotherapy followed by concurrent treatment (Arm 1) vs. immediate concurrent chemotherapy/radiotherapy (CT/RT) (Arm 2). Arm 1 consisted of vinblastine (VB), 5 mg/M2 I.V. bolus weekly, weeks 1-5 and cisplatin (DDP), 100 mg/M2 days 1 and 29, DDP 75 mg/M2, days 50, 71, and 92. Daily RT started on day 50; a total dose of 63 Gy was given in 34 fractions in 7 weeks. In Arm 2 RT started day 1; a total dose of 69.6 Gy was given in 58 fractions of 1.2 Gy bid, 5 days per week for 6 weeks with DDP 50 mg/M2 i.v. days 1 and 8, and oral VP-16 50 mg b.i.d. during the first 10 days of RT. DDP/VP-16 were repeated beginning day 29. Survival was used as the Phase II endpoint. RESULTS: Between July 1992 and February 1994, 168 patients were randomized; 162 evaluable patients had minimum follow-up of 20 months. Eighty patients were registered to Arm 1 and 82 to Arm 2. Pretreatment characteristics were distributed evenly. Arm 1 had significantly more Grade 4 hematologic toxicity (62%) than Arm 2 (33%) (p = 0.021). Acute nonhematologic Grade 3+ toxicity was also greater (p = 0.018) in Arm 2 than Arm 1 due mainly to esophagitis (38 vs. 6%; p < 0.0001). Grade 3+ late esophageal toxicity was 12% on Arm 2 compared to 3% on Arm 1 (p = 0.006). There were no differences between the two arms in compliance with protocol specifications for either RT or CT. At 1 year, 31.7% of patients had in-field progression on Arm 1 compared to 19.8% on Arm 2 (p = 0.042), but overall progression-free survival rates were nearly identical; 50 and 49% for Arms I and II, respectively, at 12 months. One-year and median survivals were 65% and 15.5 months on Arm 1 compared to 58% and 14.4 months on Arm 2. CONCLUSION: Whereas hematologic toxicity was greater in Arm 1, esophageal toxicity, both acute and late, was greater in Arm 2. Infield progression was lower in Arm 2, but overall progression rates were similar and there were no significant differences in survival between the two arms. A 3-arm randomized Phase III study is underway in the RTOG to compare sequential and concurrent CT/RT.

Antineoplastic Combined Chemotherapy Protocols↗

Impact of adding concurrent chemotherapy to hyperfractionated radiotherapy for locally advanced non-small cell lung cancer (NSCLC): comparison of RTOG 83-11 and RTOG 91-06.

A hyperfractionated radiation therapy (HFX RT) trial (1.2 Gy twice daily, b.i.d.) (HFX) for non-small cell lung cancer (NSCLC) showed that 69.6 Gy resulted in better survival than did lower total doses (Radiation Therapy Oncology Group, RTOG 83-11) and that cisplatin concurrent with irradiation improved local control and survival over RT alone (Radiation Therapy Oncology Group, RTOG 91-06). Concurrent combination chemotherapy and HFX could improve both local and systemic control. In a phase II trial (RTOG 91-06) for inoperable NSCLC, two cycles of PE were used [cisplatin 50 mg/m2 intravenously (i.v.) days 1 and 8, etoposide 50 mg orally (p.o.) b.i.d., 75 mg/day if body surface area (BSA) < 1.7 m2, days 1-14] starting on day 1 of HFX (69.6 Gy) and repeated on day 29. HFX/PE was compared with HFX (69.6 Gy) from an earlier phase II trial (RTOG 83-11). Seventy-six patients treated with HFX/PE and 203 patients who received HFX alone were compared for toxicity, response, survival, and patterns of failure. The rates of grade 4 nonhematologic toxicity were similar (3.0% for HFX/PE, 3.0% for HFX), but grade 4 hematologic toxicity occurred only with HFX/PE 56.6%. Three (3.9%) HFX/PE patients had fatal toxicity (2 pulmonary, 1 renal); 1 HFX patient had fatal esophageal toxicity. Response and metastasis rates were similar for the two treatments, but infield (p = 0.054) and overall (p = 0.04) progression-free survival rates were better with HFX/PE. Median survivals were 18.9 months with HFX/PE and 10.6 months with HFX. Two-year survival rates were 36% for HFX/PE and 22% for HFX (p = 0.014). The differences in survival between HFX/PE and HFX remained borderline statistically significant (p = 0.0593) in the multivariate model, which included weight loss, Karnofsky performance status (KPS), sex, and stage. HFX/PE is an effective regimen in patients with inoperable NSCLC, although it is considerably more toxic, and is undergoing a comparison in a three-arm randomized phase III study against induction cisplatin/vinblastine plus standard once-daily RT and against cisplatin/vinblastine concurrent with standard RT.

Administration, Oral↗

Thymic neoplasms.

Thymomas are infrequent and relatively indolent mediastinal tumors. They are usually encapsulated and readily removed. Invasive tumors, even if completely resected, require additional therapy. Although efforts have been made to relate histopathologic characteristics to outcome, the most important prognostic factors are stage and ability to achieve complete resection. The responsiveness of these tumors to chemotherapy and radiation therapy has led to combining all three modalities in a consistent sequence to derive maximal benefit from each to outcome in patients with locally advanced stage tumors.

Humans↗

Paclitaxel/carboplatin chemotherapy as primary treatment of brain metastases in non-small cell lung cancer: a preliminary report.

Chemotherapy has been rarely considered an important treatment modality for brain metastases. Based on the hypothesis that the lack of efficacy of chemotherapy, rather than the blood-brain barrier itself, may be the major hindrance to the successful chemotherapeutic treatment of brain metastases, we started a trial in which a selected group of non-small cell lung cancer patients with brain metastases received primary treatment with systemic chemotherapy. The treatment consisted of three courses of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) 225 mg/m2 given intravenously over 3 hours and carboplatin dosed to an area under the concentration-time curve of 6, with close monitoring of the lesion by computed tomography or magnetic resonance imaging of the brain after each chemotherapy course. Any radiographic or clinical evidence of progression in the brain during treatment or no improvement in the brain after three cycles of chemotherapy mandated whole brain irradiation (30 Gy in 10 fractions). Responding patients received three additional courses of chemotherapy; whole brain irradiation was given after completion of all six chemotherapy cycles. To date, five patients have been enrolled, and one has achieved partial remission both in the brain and at the extracranial site. Other patients did not achieve major objective responses either in the brain or at the extracranial sites. These preliminary results, which are consistent with the study hypothesis, support the feasibility of our approach. We therefore continue to accrue patients for this study.

Adult↗

Apoptosis and mitosis as prognostic factors in pathologically staged N1 nonsmall cell lung cancer.

PURPOSE: This study aimed to established whether spontaneous apoptosis or mitosis has prognostic value among patients with pathologically staged N1 nonsmall cell lung carcinoma (NSCLC) treated with surgical resection with or without adjuvant therapy. METHODS AND MATERIALS: Material from 173 patients who had resections between 1970 and 1988 was analyzed for apoptosis and mitosis. There were 128 men and 45 women, with a median age of 61 years. There were 86 squamous cell carcinomas (SQ), 73 adenocarcinomas (AC), 3 large-cell carcinomas (LC), 6 SQ-AC, and 5 unclassified. Patients were observed from 2 to 209 months (median 27). Actuarial methods were used to assess survival and freedom from distant metastasis. RESULTS: In NSCLC, apoptosis was found to range from 0.2% to 2.8% (median 1.0%) and mitosis from 0 to 1.8% (median 0.4%). Tumors having higher levels of apoptosis also had higher levels of mitosis (p = 0.001). The values of neither apoptosis nor mitosis depended on size, location, differentiation of tumors, age, performance status, or weight loss of patients. However, the values of apoptosis depended on tumor histology in that high values (greater than or equal to the median) were more frequent in SQ (49%) than in AC/LC (29%) (p = 0.01). The overall survival for NSCLC patients, which was 33% at 5 years, did not depend on the level of either apoptosis or mitosis. The 5-year survival of patients having SQ was higher (43%) than that of patients having AC/LC (21%) (p = 0.03). Patients with high apoptosis showed significantly better 5-year overall (p = 0.008) and DMF (p = 0.0012) survivals in the SQ group compared to the AC/LC group. High mitosis compared to low mitosis was a significantly better predictor for 5-year survival (62% vs. 29%, respectively) (p = 0.035) in the SQ. However, high mitosis was a significantly worse 5-year DMF survival predictor compared to low mitosis: 13% vs. 56%, respectively (p = 0.05) in AC/LC. In the multivariate models for AC/LC, mitosis remained a significant predictor of 5-year distant metastasis (p = 0.025) controlling for treatment groups (p = 0.042), whereas apoptosis was an independently significant predictor of 5-year distant metastasis (p = 0.010). CONCLUSION: Squamous cell histology predicted significantly better 5-year overall and DMF survivals compared to AC/LC. Apoptosis was correlated with mitosis. Although apoptosis or mitosis did not predict survival or DM, high apoptosis or mitosis predicted significantly better survival in SQ and significantly worse survival in AC/LC with regard to overall and DMF survivals. In the multivariate models for AC/LC, apoptosis alone or mitosis with variable treatment was a significant predictor of 5-year distant metastasis. Thus, pretreatment levels of apoptosis or mitosis might be useful for predicting treatment outcome of SQ and AC/LC subsets of NSCLC when analyzed separately and for predicting metastatic incidence of AC/LC.

Adenocarcinoma↗

Prognostic factors in the treatment of node-negative nonsmall cell lung carcinoma with radiotherapy alone.

PURPOSE: For patients with early stage nonsmall cell lung carcinoma (NSCLC) but medically inoperable, aggressive radiation therapy might impact on survival. METHODS AND MATERIALS: Between 1980 and 1990, 71 patients treated at MDACC by radiation therapy alone for NSCLC because of medical contradindications for surgery were analyzed. All patients had histologic or cytologic confirmation of NSCLC. The median total radiation dose was 63.23 Gy with 79% of patients receiving doses exceeding 60 Gy. The radiographic response was documented at completion of radiation therapy and 6 months after completion of radiation therapy. The median follow-up time was 36 months, ranging from 14-61 months. RESULTS: Overall survival rates at 3 and 5 years were 19 and 12%, respectively. The disease-specific survival (DSS) rates at 3 and 5 years were 44 and 32%, respectively. The DSS rates at 3 years by T-stage were: 49% for T1, 47% for T2, 26% for T3, and 32% for T4. The local control rates at 3 and 5 years were 66 and 56%, respectively. The local control rates at 3 years by T-stage were: 89% for T1, 61% for T2, 42% for T3, and 55% for T4. Univariately, the significant favorable prognostic factors for DSS were a KPS > or = 70, tumor size < or = 5 cm, no chest-wall invasion, and a radiation dose > or = 50 Gy. The significant favorable prognostic factors for local control were tumor size < or = 4 cm, no chest-wall invasion, a radiation dose > 60 Gy, and a complete response confirmed by chest x-ray at 6 months after radiotherapy (p = 0.04). Coverage of nodal drainage areas did not affect survival or local control. No lethal complications were seen, and documented symptomatic radiation pneumonitis occurred in only 7% of cases. Hence, the significant favorable prognostic factors for DSS were a KPS of > or = 70, tumor size < or = 5 cm, no chest-wall invasion, and a radiation dose > or = 50 Gy. The significant favorable prognostic factors for local control were tumor size of < or = 4 cm, no chest-wall invasion, a radiation dose > 60 Gy, and a complete response confirmed by chest x-ray at 6 months after radiotherapy. Multivariate analysis showed that the most important prognostic factor for DSS was KPS, and the most important prognostic factor for local control was radiation dose. CONCLUSIONS: Patients with a KPS of > or = 70, a tumor size < 5 cm, and no chest-wall invasion would benefit most from treatment with radiation alone to doses exceeding 60 Gy. This patient group represents the best sample for studying the benefit of conformal radiotherapy.

Carcinoma, Non-Small-Cell Lung↗

The use of radiochromic film to measure dose distributions resulting from high dose rate 192Iridium single catheter treatments.

PURPOSE: Radiochromic film was used to measure and compare the dose distributions parallel to a high dose rate (HDR) 192Iridium (192Ir) brachytherapy afterloading catheter that resulted from optimized treatment plans using various combinations of prescribed dose magnitude and location as well as source spacing. METHODS AND MATERIALS: Differences exist among clinical investigators for specification of the magnitude and location of prescribed treatment dose for brachytherapy irradiations using HDR 192Ir afterloading. Typical prescriptions for endobronchial irradiation include 5 to 10 Gy at 10 mm or 15 Gy at 6 mm measured from the center of the afterloading catheter. The dose distributions that result from these irradiations are very difficult to quantify by conventional dosimetry methods. This study used radiochromic film to measure the dose distributions resulting from optimized treatment plans for source dwell position separations of 2.5 or 5.0 mm and for a prescribed treatment dose of either 15 Gy at 6 mm or 5 Gy at 10 mm, conditions that have been used at M. D. Anderson Cancer Center for the treatment of endobronchial lesions. An acrylic phantom was designed to allow for measurement of the dose distributions at 0.95 mm (catheter surface), 6 mm, and 10 mm from and parallel to the catheter for sources positioned along either 20 or 80 mm of the catheter. RESULTS: Radiochromic film is shown to be a suitable quality assurance and dosimetry modality for the measurement of the dose distribution along an afterloading catheter resulting from an HDR I92Ir source. Each of the treatment plans was about equally effective in being able to produce a uniform dose distribution at their respective planned target distances. Differences were more apparent when comparing the dose distributions at nontargeted distances. On the catheter surface the dose was very nonuniform and in the case of 2.5 mm source spacing along 20 mm of catheter with target dose planned to 10 mm, the central minimum dose was only 13 to 24% of the dose opposite to the most proximal and distal sources. The absolute doses measured at equivalent distances for the 15 Gy planned to 6 mm treatments are about 1.3 to 1.5 times higher than those measured for the 5 Gy planned to 10 mm treatments. It was also observed that the lateral positioning of the encapsulated source within the afterloading catheter can contribute to dose differences about the catheter that are greatest for measurements made in contact with the catheter surface (24 to 40%) but may also be large at the treatment planning distances of 6 (0 to 15%) and 10 mm (0 to 9%). CONCLUSION: At their respective treatment planning distances of 6 or 10 mm, each of the treatment plans produced dose distributions of comparable uniformity. Against the catheter, relatively more uniform dose distributions with higher minimum doses were obtained for (a) dose prescription at 6 mm, rather than at 10 mm; (b) source separation of 2.5 mm, rather than 5.0 mm (except for a 20 mm active catheter length with dose planned to 10 mm); and (c) longer active length of the catheter of 80 mm, rather than 20 mm.

Brachytherapy↗

Retrovirus-mediated wild-type p53 gene transfer to tumors of patients with lung cancer.

A retroviral vector containing the wild-type p53 gene under control of a beta-actin promoter was produced to mediate transfer of wild-type p53 into human non-small cell lung cancers by direct injection. Nine patients whose conventional treatments failed were entered into the study. No clinically significant vector-related toxic effects were noted up to five months after treatment. In situ hybridization and DNA polymerase chain reaction showed vector-p53 sequences in posttreatment biopsies. Apoptosis (programmed cell death) was more frequent in posttreatment biopsies than in pretreatment biopsies. Tumor regression was noted in three patients, and tumor growth stabilized in three other patients.

Aged↗

Combined Chemotherapy and Radiation Therapy in Surgically Unresectable Regionally Advanced Non-Small Cell Lung Cancer.

There have been increasing reports suggesting that combined treatment modality is superior to one modality approach in regard to median and 2-year survivals, and local control for patients with locally advanced unresectable (stage III) non-small cell lung cancer. However, there are five major issues to be discussed before the above conclusion will be drawn. First, the staging system for lung cancer is not perfect and extent of metastatic workup is controversial for patients with locally advanced unresectable non-small cell lung cancer. It is difficult to compare studies which have not mentioned the proportion of stage IIIA to stage IIIB nor completeness of staging workup. The second controversial area is selection of patients to be treated by combined modality. Third, definition of unresectability changes depending on the surgeon's aggressiveness, skills, experience, and back-up system, including other specialty groups and facilities as well as the patient's willingness and physical fitness. Fourth, optimal sequences of combined modalities are still under investigation. Finally, rates of toxicity of the combined modality need to be reported as well as efficacy of treatment.

Journal Article↗

Endobronchial brachytherapy with high-dose-rate remote afterloading for recurrent endobronchial lesions.

PURPOSE: To evaluate toxicity and efficacy of endobronchial brachytherapy with high-dose-rate (HDR) after-loading of iridium-192 for recurrent endobronchial lesions. MATERIALS AND METHODS: From 1988 to 1993, 81 patients with lung cancer previously treated with external beam radiation therapy were treated with palliative HDR endobronchial brachytherapy for symptoms due to relapse or persistent tumor of endobronchial bronchogenic origin. For most patients, Ir-192 was delivered in a dose of 3,000 cGy at 6 mm in two fractions over 2 weeks. RESULTS: Sixty-eight patients (84%) achieved some response: Twenty-six (32%) had excellent, 25 (31%) had moderate, and 17 (21%) had minimal symptomatic improvement with HDR endobronchial brachytherapy. Eleven patients had no change, and two became worse. The median duration of responses was 4.5 months. Those patients with an excellent response had a significantly better survival (13.3 months) compared with that of the other patients (5.4 months) (P = .01). There were two fatal complications, which were due to fistula and tracheal malacia. CONCLUSION: HDR endobronchial brachytherapy is an effective method to relieve airway obstruction promptly for patients with recurrent endobronchial lesions and may be considered as a boost for obstructive lesions before chemotherapy and external beam radiation therapy.

Brachytherapy↗

The Y chromosome region essential for spermatogenesis.

We analyzed DNA from 153 Japanese men with azoospermia or severe oligozoospermia whose Y chromosomes were cytogenetically normal. A total of 23 loci on the Y chromosome were examined: 15 loci within interval 6 including YRRM1 and DAZ, and 8 loci outside interval 6. Microdeletions were observed in 20 individuals. All deletions involved at least one locus within interval 6. The YRRM1 gene deletion was found in 4 patients, of whom 2 also lacked the SMCY gene. The remaining 16 individuals shared the absence of 10 loci between DYS7C and DYS239 including the DAZ gene. Among them, 13 were azoospermic while 3 showed a little sperm production, indicating that the common deletion resulted in phenotypic diversity. Since there is no region commonly deleted in all patients, azoospermia caused by deletion of the Y chromosome long arm may be genetically heterogeneous.

Adult↗

Concurrent chemoradiation therapy with oral etoposide and cisplatin for locally advanced inoperable non-small-cell lung cancer: radiation therapy oncology group protocol 91-06.

PURPOSE: Patients with locally advanced inoperable non-small-cell lung cancer (NSCLC) have a poor clinical outcome. We conducted a prospective study to evaluate the merit of chemotherapy administered concurrently with hyperfractionated thoracic radiation therapy. PATIENTS AND METHODS: Seventy-nine patients with inoperable NSCLC were enrolled onto a multicenter phase II trial of concurrent chemoradiation therapy. Treatment consisted of two cycles of oral etoposide 100 mg/d (50 mg/d if body-surface area [BSA] < 1.70 m2), intravenous cisplatin 50 mg/m2 on days 1 and 8, and hyperfractionated radiation therapy 5 days per week (1.2 Gy twice daily > 6 hours apart; total 69.6 Gy). RESULTS: Seventy-six assessable patients with a Karnofsky performance status > or = 60 and adequate organ function who had received no prior therapy were evaluated for clinical outcome and toxic effects. After a minimum follow-up duration of 21 months, the 1- and 2-year survival rates and the median survival duration were 67%, 35%, and 18.9 months overall; they were 70%, 42%, and 21.1 months for patients with weight loss of < or = 5%. Toxicity was significant; 57% developed grade 4 hematologic toxicity, 53% grade 3 or 4 esophagitis, and 25% grade 3 or 4 lung toxicity. However, only 6.6% of patients had grade 4 or lethal nonhematologic toxicity, which included three treatment-related deaths (two of pneumonitis and one of renal failure). CONCLUSION: Concurrent chemoradiation therapy with oral etoposide and cisplatin plus hyperfractionated radiation therapy is feasible. The survival outcome from this regimen compares favorably with that of other chemoradiation trials and even of multimodality trials that have included surgery.

Administration, Oral↗

Prospective study of combination chemotherapy with cyclophosphamide, doxorubicin, and cisplatin for unresectable or metastatic malignant pleural mesothelioma.

BACKGROUND: This study was designed to determine the efficacy and side effects of a combination of cyclophosphamide (C), doxorubicin (D), and cisplatin (P) in patients with inoperable, unresectable, or metastatic malignant pleural mesothelioma. METHODS: Twenty-three patients with unresectable or metastatic malignant pleural mesothelioma were entered onto the study. The median age was 62 years (range, 42-74 years); there were 20 males and 3 females; the median performance status was 1 (Zubrod's scale). The histologic types included epithelial (14 patients), sarcomatoid (4 patients), unclassified (4 patients), and mixed type (1 patient). Twenty patients were known to have been exposed to asbestos and 3 were not. All patients were treated with the following starting dose of chemotherapy: a cycle comprised of C, 500 mg/m2 intravenously, day 1; D, 50 mg/m2 intravenously, day 1; and P, 80 mg/m2 intravenously, day 1 every 3 weeks. The cisplatin dose was reduced to 50 mg/m2 for the subsequent courses. For the assessment of tumor response, all patients had computed tomography scans of the chest after each three cycles of chemotherapy. RESULTS: Overall, 7 of 23 patients (30%) had partial responses (durations of responses [weeks]: 158+, 91+, 70+, 41+, 40, 39, 25), three had minor responses, and 14 had stable or progressive disease. One partial responder later underwent surgical resection and no viable tumors cells were found in the pathologic specimen. All patients have stopped treatment, and eight are still alive. The most common side effect was granulocytopenia (grade 4, 52%; grade 3, 17%). Other hematologic side effects were modest. Nonhematologic side effects included mild to moderate nausea and vomiting, neutropenic fever (three patients), peripheral neuropathy (one patient), and congestive heart failure (one patient). The overall median duration of survival was 60 weeks. CONCLUSION: Combination chemotherapy with CDP was well tolerated and had significant activity against unresectable or metastatic malignant pleural mesothelioma. The median duration of responses was 60 weeks; however, the survival rate was far from satisfactory. Continued development of new approaches including the biologic understanding of tumor development and testing new agents is warranted.

Adult↗

Altered fractionation and extended-field irradiation of carcinoma of the cervix.

Conventional radiotherapy for treatment of carcinoma of the cervix consists of five daily fractions of 1.80-2.00 Gy, 5 days/week, up to 40.00-50.00 Gy, followed by intracavitary brachytherapy to complete a paracentral dose ranging from 70 to 90 Gy and a lateral pelvic wall dose ranging from 50 to 60 Gy. This results in tumor control in the pelvis for at least 91% of patients with Stage IB disease. However, survival rates at 5-year follow-up have ranged from 49% to 69% for patients with Stage III disease and 25% to 34% for patients with Stage IVA disease. Attempts to improve clinical results for patients with more advanced stages of disease have included hypofractionated and hyperfractionated radiotherapy, accelerated fractionation, and concomitant boost. However, no improvement of tumor control or survival has been obtained. Hyperfractionated external pelvic radiation remains undefined as a method of improving results. Extended-field prophylactic irradiation of the paraaortic lymph nodes has shown significant value in a study group setting. Early diagnosis and prevention continue to be the most promising approaches in the control of carcinoma of the cervix.

Female↗