melphalan and Carcinoma

Pulmonary metastasectomy is a widely accepted treatment for many patients with pulmonary metastases from various solid tumors. Nevertheless, 5-year survival is disappointing, with rates of 25-40%, and many patients develop recurrences. Isolated lung perfusion (ILuP) is a promising new technique to deliver high-dose chemotherapy to the lungs, while minimising systemic toxicities. This procedure is technically safe and feasible; however, clinical value and efficacy remain unclear. The aim of this paper is to give a review of literature on ILuP in humans, and to describe the development of the perfusion procedure in our institute.

Topics: Animals; Antineoplastic Agents; Blood Transfusion, Autologous; Carcinoma; Chemotherapy, Cancer, Regional Perfusion; Clinical Trials, Phase I as Topic; Combined Modality Therapy; Drug Screening Assays, Antitumor; Embolism, Air; Equipment Design; Extracorporeal Membrane Oxygenation; Feasibility Studies; Humans; Hydroxyethyl Starch Derivatives; Hyperthermia, Induced; Intraoperative Complications; Isotonic Solutions; Lung Neoplasms; Melphalan; Pilot Projects; Rheology; Ringer's Lactate; Sarcoma; Solutions; Temperature; Treatment Outcome

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Carcinoma; Clinical Trials as Topic; Combined Modality Therapy; Female; Hematopoietic Stem Cell Transplantation; Humans; Melphalan; Ovarian Neoplasms

Poor survival rates of ovarian carcinoma have continued to be a cause of grave concern over decades and led to growing attention and alert in recent years. Promising results have already been recorded. More knowledge of important factors with relevance to prognosis has been helpful in unitising large-scale therapeutic studies for better comparability, a desire which had been unfulfilled in the past. Close interdisciplinary cooperation between gynaecologists, radiotherapists, and chemotherapists proved to be essential to optimum programmes of therapy. Persistent basic research for better understanding of biological behaviours of ovarian carcinomas and of so far unknown factors of prognosis and persistent efforts for earlier diagnosis of ovarian carcinoma are just as important. This is the only way to more effective control of the disease which still is, diagnostically and therapeutically, one of the major problems in gynaecology.

Topics: Carcinoma; Chlorambucil; Cyclophosphamide; Cystadenocarcinoma; Female; Humans; Melphalan; Mesonephroma; Neoplasm Staging; Ovarian Neoplasms; Prognosis; Thiotepa

Topics: Adenocarcinoma; Alkylating Agents; Antineoplastic Agents; Breast Neoplasms; Carcinoma; Carcinoma, Bronchogenic; Carmustine; Cyclohexanes; Cyclophosphamide; Cytarabine; Drug Therapy, Combination; Hodgkin Disease; Humans; Hydroxyurea; Leukemia, Lymphoid; Leukemia, Myeloid; Lymphoma; Melanoma; Melphalan; Multiple Myeloma; Nitrosourea Compounds; Prednisone; Vincristine

Topics: Carcinoma; Chlorambucil; Cyclophosphamide; Female; Genital Neoplasms, Female; Humans; Hysterectomy; Lymph Node Excision; Melphalan; Ovarian Neoplasms; Progestins; Radiotherapy, High-Energy; Thiotepa; Uterine Cervical Neoplasms; Uterine Neoplasms

Topics: Adenocarcinoma; Ascites; Carcinoma; Cyclophosphamide; Female; Fluorouracil; Humans; Injections, Intravenous; Melphalan; Nitrogen Mustard Compounds; Ovarian Neoplasms; Thiotepa

To improve isolated hepatic perfusion (IHP), we performed a phase I dose-escalation study to determine the optimal oxaliplatin dose in combination with a fixed melphalan dose.. Between June 2007 and July 2008, 11 patients, comprising of 8 colorectal cancer and 3 uveal melanoma patients and all with isolated liver metastases, were treated with a one hour IHP with escalating doses of oxaliplatin combined with 100 mg melphalan. Samples of blood and perfusate were taken during IHP treatment for pharmacokinetic analysis of both drugs and patients were monitored for toxicity, response and survival.. Dose limiting sinusoidal obstruction syndrome (SOS) occurred at 150 mg oxaliplatin. The areas under the concentration-time curves (AUC) of oxaliplatin at the maximal tolerated dose (MTD) of 100 mg oxaliplatin ranged from 11.9 mg/L h to 16.5 mg/L h. All 4 patients treated at the MTD showed progressive disease 3 months after IHP.. In view of similar and even higher doses of oxaliplatin applied in both systemic treatment and hepatic artery infusion (HAI), applying this dose in IHP is not expected to improve treatment results in patients with isolated hepatic metastases.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Chemotherapy, Cancer, Regional Perfusion; Cohort Studies; Colorectal Neoplasms; Female; Humans; Liver Neoplasms; Male; Maximum Tolerated Dose; Melanoma; Melphalan; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Prospective Studies; Treatment Outcome; Uveal Neoplasms

To evaluate the efficacy and safety of multiple cycles of high-dose carboplatin and paclitaxel and one consolidation cycle of high-dose melphalan with all cycles supported by hematopoietic stem cells and cytokine, in previously untreated patients with optimally debulked stage III epithelial ovarian cancer.. Patients had histologically documented epithelial ovarian cancer and optimal initial cytoreductive surgery. No prior chemotherapy was permitted. Adequate performance status, bone marrow, hepatic, and renal function was required. After being mobilized with cyclophosphamide 3 g/m(2), paclitaxel 300 mg/m(2), and filgrastim 5 microg/kg/day, peripheral blood stem cells (PBSC) were collected by leukapheresis. Patients received three cycles of carboplatin AUC 15 mg. min/ml iv, paclitaxel 250 mg/m(2), and PBSC with filgrastim every 28 days, followed by one cycle of melphalan 140 mg/m(2) and hematopoietic support.. Nine patients entered the trial and received all planned cycles of chemotherapy. Of the eight patients who consented to surgical reassessment upon completing therapy, four had residual small-volume macroscopic disease, three had microscopic residual disease, and one had pathologic complete response. The estimated probability of a pathologic complete response was 12.5% (95% confidence interval: 0.3-52.7%). Hematologic toxicity was severe but manageable. Eleven of 45 cycles (24.4%) resulted in hospital admission for neutropenic fever, dehydration +/- diarrhea, syncope, or shortness of breath and pain secondary to tense ascites.. The low pathological complete response rate did not justify toxicity; thus, the study was closed. High-dose chemotherapy as first-line treatment for epithelial ovarian cancer remains experimental and should be restricted to clinical trials.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma; Combined Modality Therapy; Cyclophosphamide; Dose-Response Relationship, Drug; Drug Administration Schedule; Epithelial Cells; Female; Filgrastim; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Humans; Melphalan; Middle Aged; Neoplasm Staging; Ovarian Neoplasms; Paclitaxel; Peripheral Blood Stem Cell Transplantation; Pilot Projects; Recombinant Proteins

Although high-dose chemotherapy (HDC) with stem cell rescue for the treatment of women with metastatic breast cancer (MBC) is currently a controversial strategy, we report the long-term outcomes of women undergoing high-dose therapy for MBC over the past 12 years while participating in a sequence of research studies transitioning between a single to a double intensification approach. Univariate and multivariate analyses provide a framework to understand the prognostic factors important for event-free and overall survival. Between May 1988 and April 1998, we enrolled 188 women with MBC into 3 trials of previously reported sequential transplantation strategies. Trial I (long induction/single transplantation) accepted 62 women in partial or complete response to an unspecified induction therapy and treated them with high-dose CTCb (cyclophosphamide, thiotepa, and carboplatin) supported by marrow or peripheral blood progenitor cells (PBPC). Trial II (long induction/double transplantation) accepted 68 women in partial or complete response to an unspecified induction therapy, and mobilized stem cells with 2 cycles of AF (doxorubicin and 5-fluorouracil) with granulocyte colony-stimulating factor (G-CSF). These women then received 1 cycle of high-dose single-agent melphalan followed 3 to 5 weeks later by CTCb, each with marrow or PBPC support. Trial III (short induction/double transplantation) enrolled 58 women prior to chemotherapy treatment for metastatic disease. Induction/mobilization consisted of 2 cycles given 14 days apart of doxorubicin and G-CSF. In contrast to trials I and II, patients with stable disease or better response to induction were eligible to proceed ahead with 2 cycles of HDC, 1 being CTCb and the other being dose escalated paclitaxel together with high-dose melphalan (TxM). These 2 HDC regimens were administered 5 weeks apart. TxM was given first in 32 patients and CTCb was given first in 26 patients. The median follow-up periods for trials I, II, and III were 98, 62, and 39 months from the initiation of induction chemotherapy and 92, 55, and 36 months from last high-dose therapy, respectively. The patient characteristics upon entry into these trials were similar. Important differences were that only those patients achieving a partial response or better to induction therapy were enrolled and analyzed for trials I and II, but all patients were analyzed on an intent-to-treat basis for trial III, including those who did not receive intensificat

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Carboplatin; Carcinoma; Combined Modality Therapy; Cyclophosphamide; Disease-Free Survival; Doxorubicin; Drug Administration Schedule; Estrogens; Female; Fluorouracil; Follow-Up Studies; Granulocyte Colony-Stimulating Factor; Humans; Life Tables; Melphalan; Methotrexate; Middle Aged; Multivariate Analysis; Neoplasm Metastasis; Neoplasms, Hormone-Dependent; Paclitaxel; Peripheral Blood Stem Cell Transplantation; Progesterone; Prognosis; Proportional Hazards Models; Remission Induction; Survival Analysis; Thiotepa; Time Factors; Treatment Outcome

The primary purpose of this study was to establish the maximum tolerated dose (MTD) of intravenous melphalan in combination with paclitaxel and cisplatin plus granulocyte-colony stimulating factor (G-CSF) in patients with suboptimal advanced epithelial ovarian carcinoma or primary peritoneal carcinoma.. Patients with suboptimal (>2 cm residual tumor) Stage III or Stage IV epithelial ovarian carcinoma or peritoneal carcinoma were eligible for this Phase I study. In the first stage of the study, the doses of paclitaxel and cisplatin were fixed at 135 mg/m(2) and 75 mg/ m(2), respectively, and the dose of intravenous melphalan was escalated in consecutive cohorts of 3-6 patients depending on toxicity. The planned dose escalation levels of melphalan were 6 mg/m(2), 10 mg/m(2), and 14 mg/m(2). In the second stage of the study, the doses of cisplatin and melphalan were fixed at 75 mg/m(2) and the MTD level, respectively, and the dose of paclitaxel was escalated. The planned dose escalation levels of paclitaxel were 150 mg/m(2), 175 mg/m(2), 200 mg/m(2), 225 mg/m(2), and 250 mg/m(2). G-CSF was administered for 12-19 days with each cycle, and cycles were repeated every 4 weeks for a total of 6 cycles. Other end points included clinical or surgical response, progression free survival, and survival.. Between January 1993 and May 1996, 34 women with untreated advanced stage epithelial ovarian carcinoma or primary peritoneal carcinoma were treated with 192 cycles of therapy. The MTD of melphalan was 10 mg/m(2), with the dose-limiting toxicity being thrombocytopenia. Paclitaxel was escalated to a dose level of 200 mg/m(2) with a toxicity rate of < 33%. The clinical response rate was 80% in 29 patients with measurable disease. Of 11 patients who underwent second-look surgery, 5 (45%) had a surgical pathologic complete response. The median progression free survival was 16.8 months and the median survival was 32.8 months.. The combination of intravenous melphalan, paclitaxel, and cisplatin was found to have acceptable toxicity and good activity. A Phase II study of this combination appears to be warranted.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Cisplatin; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Granulocyte Colony-Stimulating Factor; Humans; Infusions, Intravenous; Melphalan; Middle Aged; Ovarian Neoplasms; Paclitaxel; Peritoneal Neoplasms; Treatment Outcome

The purpose of this study was to develop a high-dose chemotherapy (HDC) and peripheral blood stem cell (PBSC) regimen for treatment of patients with ovarian carcinoma that could be administered in an outpatient setting. Fourteen patients with advanced ovarian (n = 9) or breast (n = 5) carcinoma, who had failed conventional chemotherapy, were entered into a dose-escalation trial to determine the maximum tolerated dose (MTD) of carboplatin that could be administered with fixed doses of melphalan (160 mg/m2) and mitoxantrone (50 mg/m2). Twenty-five additional patients were included in a phase II trial at the MTD. Two of two patients had grade 4 severe regimen-related toxicities (RRT), one fatal, at a dose level of 1600 mg/m2. Two of 29 patients (6.9%) treated at the MTD (carboplatin, 1400 mg/m2) died of RRT. All three patients who died of toxicity had a calculated AUC for carboplatin >30 mg/ml/min. Thirty-one patients with ovarian cancer who had failed chemotherapy were treated, 24 at the MTD. Fourteen of 20 patients (70%) with ovarian carcinoma with evaluable disease achieved a CR and seven (35%) are alive disease-free a median of 20 months (range, 7-26). Five of seven patients with ovarian cancer who had failed chemotherapy but were rendered clinically disease-free following surgery survive without progression a median of 13 months (range, 9-19). Eight of 16 (50%) platinum-resistant and 4/12 (33%) platinum-sensitive patients with ovarian cancer survive disease-free.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Diseases; Breast Neoplasms; Carboplatin; Carcinoma; Cerebral Hemorrhage; Combined Modality Therapy; Disease-Free Survival; Female; Hematopoietic Stem Cell Transplantation; Humans; Life Tables; Lung Diseases, Interstitial; Melphalan; Middle Aged; Mitoxantrone; Ovarian Neoplasms; Renal Insufficiency; Salvage Therapy; Treatment Outcome

Following surgical debulking, most patients with international Federation of Gynecology and Obstetrics (FIGO) Stage III or IV carcinoma of the ovary receive treatment with combination chemotherapy. However, the optimal postsurgical therapy for ovarian carcinoma remains to be defined.. To define better the role of initial therapy with a cisplatin-based chemotherapy regimen, the Eastern (Cooperative Oncology Group (ECOG) initiated a randomized, Phase III trial, EST 2878, comparing initial therapy with a single, orally administered alkylating agent, melphalan, versus a complex regimen employing cyclophosphamide, hexamethylmelamine, doxorubicin, and cisplatin (CHAD). Women who failed treatment with melphalan were crossed-over to treatment with CHAD minus the cyclophosphamide (HAD). Study endpoints included response to therapy, time to treatment failure, and overall survival.. Between October, 1978, and November, 1980, EST 2878 accrued 253 patients with advanced epithelial carcinoma of the ovary. There were 118 eligible patients initially treated with melphalan and 126 with CHAD. Two patients experienced lethal toxicities, including gastrointestinal hemorrhage (1 patient) and neutropenic sepsis (1 patient), and 22 patients experienced life-threatening toxicities, including hematologic toxicity (21 patients) and anaphylaxis (1 patient). Response to treatment and clinical complete response rates were higher in women receiving CHAD (60% and 38%, respectively) versus melphalan (42% and 21%, respectively) (P = 0.037 and P = 0.024, respectively), but these differences were confined to women older than 50 years of age. Likewise, time to treatment failure was significantly longer in women receiving CHAD (P = 0.014), but the difference was again confined to women older than 50 years of age and to women suboptimally debulked at the time of surgery. Survival did not differ between the two arms (median survivals of 17.5 months with initial melphalan therapy and 19.5 months with CHAD), probably because women treated initially with melphalan received salvage therapy with HAD). Twenty-three patients survived longer than 10 years. Among 18 long term survivors who had retrospective pathologic review, 8 had borderline tumors of the ovary.. In women with advanced ovarian cancer, initial therapy with a cisplatin-based combination chemotherapy regimen resulted in higher clinical complete response rates and longer time to failure compared with initial therapy with a single, oral alkylating agent; however, the benefits of this approach were confined to women older than 50 years of age at diagnosis, and there was no significant difference in survival.

Topics: Adult; Aged; Altretamine; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Cisplatin; Cross-Over Studies; Cyclophosphamide; Disease-Free Survival; Doxorubicin; Female; Follow-Up Studies; Humans; Melphalan; Middle Aged; Neoplasm Staging; Ovarian Neoplasms; Survival Rate; Time Factors

Utilization of alpha-tumor necrosis factor (alpha-TNF) in clinical practice is limited by severe general side effects. Very promising results with low toxicity were reported with administration of alpha-TNF by isolation perfusion in extracorporeal circulation.. From December 1991 to November 1992, 14 patients underwent perfusion with alpha-TNF (2-4 mg, total dose), gamma-interferon (1.5 x 10(6) IU), and melphalan (10 mg/l/perfused limb). Twelve patients presented in-transit metastases of the limbs, one patient, a clear cell sarcoma of the hand, and one patient, a wide spindle cell carcinoma of the thigh. Perfusion lasted 90 minutes and was conducted in mild hyperthermia (38-40.5 degrees C, muscle temperature).. Nine complete regressions and four stable diseases were recorded. In one case, a reliable evaluation of response was not possible for diffused tissue necrosis. Five patients relapsed or progressed locally from 3 to 4 months after surgery, five presented distant localizations from 2 to 7 months after surgery, and one died of disease 6 months after perfusion. Twelve patients are alive, seven without evidence of disease. A septic-like shock syndrome was observed in all patients and required administration of dopamine, dobutamine, or noradrenaline. One patient died 30 days after perfusion from a multiorgan-failure syndrome, likely due to alpha-TNF. The follow-up time ranges from 4 to 15 months (median, 6).. The preliminary, impressive results reported in other series were not completely confirmed in this study adopting the same treatment scheme. Further clinical experience and biologic data are needed to state the real efficacy of the approach and to reduce the severe general toxicity consistently associated with this type of treatment.

Topics: Adult; Aged; Arm; Carcinoma; Chemotherapy, Cancer, Regional Perfusion; Female; Humans; Interferon-gamma; Leg; Male; Melanoma; Melphalan; Middle Aged; Pilot Projects; Sarcoma; Skin Neoplasms; Soft Tissue Neoplasms; Tumor Necrosis Factor-alpha

Long-term follow-up was obtained on 726 women with advanced ovarian carcinoma (suboptimal stage III and stage IV) who had received primary chemotherapy on two Gynecologic Oncology Group (GOG) protocols between 1976 and 1982. The first study compared melphalan alone versus melphalan plus hexamethylmelamine versus cyclophosphamide plus doxorubicin (CA). The second study evaluated the same CA regimen with or without cisplatin. Eligibility for the two studies was the same. At last contact, 76 patients were alive. In a multivariate analysis, cell type other than clear cell or mucinous, cisplatin-based treatment, good performance status, younger age, lower stage, clinically nonmeasurable disease, smaller residual tumor volume, and absence of ascites were favorable characteristics for overall survival (P less than .05). Second-look laparotomy was negative significantly more often among those with endometrioid tumors; there were no negative second-look laparotomies among those with mucinous or clear cell tumors. There were 30 patients with suboptimal stage III disease who had a negative second-look laparotomy; 18 (60%) have experienced recurrence, and 13 (43%) have died. Although cisplatin treatment was beneficial, new treatments are clearly needed.

Topics: Adult; Aged; Altretamine; Analysis of Variance; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Cyclophosphamide; Doxorubicin; Female; Follow-Up Studies; Humans; Melphalan; Middle Aged; Ovarian Neoplasms; Prognosis; Regression Analysis; Reoperation; Survival Rate

Fifty consecutive patients with recurrent and metastatic endometrial carcinoma were treated with melphalan, 5-fluorouracil, and medroxyprogesterone acetate with or without tamoxifen as first-line chemotherapy. The objective response rate was 48%, with 20% complete responses. The estimated median progression-free survival time was only five months (0.5 to 65 months) with estimated two- and five-year progression-free survival rates of 16 and 13%, respectively. The estimated median progression-free survival time was 24 months for complete responders; the progression-free survival times were significantly longer than the survival times (median = four months) for all other patients (P = .0002). Whether or not the addition of cytotoxic chemotherapy to progesterone hormonal therapy for metastatic endometrial carcinoma lengthens survival time is still open to question.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Female; Fluorouracil; Humans; Medroxyprogesterone; Melphalan; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Prospective Studies; Random Allocation; Tamoxifen; Thrombocytopenia; Uterine Neoplasms

A prospective randomized trial was carried out in 153 patients with stage III malignant epithelial tumours for comparing the effects of irradiation or combination of chemotherapy and irradiation on prognosis and operability. No significant differences between these two treatment modalities were found. Of the patients primarily considered inoperable were 41 per cent operated upon after preoperative treatment. Minimum residual disease (0 to less than or equal to 2 cm) occurred in 38 per cent of the primarily operated and in 31 per cent of those operated upon after preoperative treatment. Preoperative irradiation in primarily inoperable patients enabled more effective surgical measures at relaparotomy. The size of the residual tumour after surgery and the tumor grade influenced the survival.

Topics: Carcinoma; Clinical Trials as Topic; Female; Humans; Laparotomy; Melphalan; Neoplasm Recurrence, Local; Neoplasm Staging; Ovarian Neoplasms; Prognosis; Radiotherapy Dosage; Random Allocation

A multimodality treatment program has been applied to ovarian carcinoma at the Johns Hopkins Hospital since August 1975. Forty-nine patients were subdivided into 23 patients with maximally resected Stage III micrometastatic, and 26 patients with significant retained disease, 20 with Stage III macrometastatic and 6 with Stage IV. After initial pilot studies, those patients with minimally retained disease entered a randomized prospective study. Antiovarian antiserum was used in one arm of the study; in both study arms colloidal P-32, delayed split whole abdominal irradiation, and maintenance melphalan were used. For the 23 patients with micrometastatic disease the cumulative survival and survival without evidence of disease at four years is 78 and 34% respectively. Twenty-six patients with macrometastatic disease were treated with or without intraperitoneal antiserum and multiagent chemotherapy; their cumulative one year survival is 50%. The lack of significant toxicity of intraperitoneal antiovarian antiserum and the results of multimodality therapy indicate the feasibility of this therapeutic approach to further improve ovarian cancer therapy.

Topics: Adenocarcinoma, Mucinous; Altretamine; Antibodies, Neoplasm; Carcinoma; Cisplatin; Clinical Trials as Topic; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Female; Humans; Melphalan; Ovarian Neoplasms; Ovary; Phosphorus Radioisotopes; Prospective Studies; Random Allocation

Two consecutive studies were undertaken in patients with advanced adenocarcinoma of the ovary to compare melphalan, adriamycin and 5-fluorouracil (MAF) with cyclophosphamide, adriamycin and 5-fluorouracil (CAF). Twenty-one patients received MAF and 19 received CAF. The objective response rate was 35% for MAF and 62% for CAF patients, and complete remission occurred in 23% of MAF, and in 56% of CAF, patients. These differences were not statistically significant. In both groups, complete remission had a statistically significant and favourable influence on survival. Toxic effects were predominantly haemopoietic and gastrointestinal, MAF having a significantly greater thrombocytopenic potential than CAF, but over-all tolerance was good on both protocols. MAF and CAF are comparable and effective combinations for the treatment of advanced ovarian cancer, but do not demonstrate superiority to single alkylating agent therapy or to other combinations. This emphasizes the continuing need for well designed randomized trials comparing single alkylating agents with combinations of known active agents.

Topics: Antineoplastic Agents; Bone Marrow Diseases; Carcinoma; Clinical Trials as Topic; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Female; Fluorouracil; Humans; Leukemia; Melphalan; Ovarian Neoplasms

The objectives of the initial surgical procedure in patients with common epithelial carcinomas of the ovary are determination of the intraabdominal extent of the cancer and the reduction of tumor masses to the smallest residuum before initiating further therapy. Since ovarian cancer is a disease of the entire abdominal cavity, biopsy of selected sites will often detect unsuspected involvement by microscopic foci of metastatic carcinoma. Tumor-reductive surgery resulting in a small tumor residuum before initiating chemotherapy is thought to improve the changes for inducing a complete response. The retroperitoneal operative approach enhances the surgeon's effort to remove tumor bulk. Between July 1, 1972, and September 1, 1978, 104 patients with FIGO Stage III or IV carcinomas of the ovary were treated with melphalan. The conditions of 38 patients were evaluated by second-look laparotomy. This analysis attempts to define tumor-reductive surgery and relates the outcome of the results of the operative procedure to patients treated with melphalan.

Topics: Adult; Carcinoma; Clinical Trials as Topic; Female; Humans; Laparotomy; Lymphatic Metastasis; Melphalan; Methods; Middle Aged; Ovarian Neoplasms; Prospective Studies; Random Allocation

The results of a national clinical trial to compare combination and sequential chemotherapy for stage III or IV ovarian cancer are reported. Of the 253 patients from 16 centres across Canada who were admitted to the trial 13 were excluded from the analysis. All the patients were observed for 2 to 5 years from entry into the trial. There were no differences in response to therapy or in survival between the patients treated with melphalan followed by 5-fluorouracil and then by methotrexate in high dosage and the patients treated with the same agents in combination. Patients with minimal residual disease after resection of stage III ovarian cancer had a good prognosis. Other favourable prognostic factors were age (less than 55 years), performance status (90% or 100% on the Karnofsky scale) and histologic grade of the tumour.

Topics: Adult; Aged; Antineoplastic Agents; Canada; Carcinoma; Clinical Trials as Topic; Drug Administration Schedule; Drug Therapy, Combination; Female; Fluorouracil; Humans; Melphalan; Methotrexate; Middle Aged; Ovarian Neoplasms

Topics: Antineoplastic Agents; BCG Vaccine; Breast Neoplasms; Carcinoma; Clinical Trials as Topic; Colonic Neoplasms; Cyclophosphamide; Drug Therapy, Combination; Female; Fluorouracil; Humans; Melphalan; Methotrexate; Mycobacterium bovis; Neoplasm Metastasis; Postoperative Care; Semustine; Vincristine

The therapeutic effects of adriamycin and of melphalan in patients with advanced carcinoma of the ovary were tested in a prospective randomized study. Complete and partial remission occurred in eight of 19 patients treated with adriamycin and in four of 20 patients given melphalan. The difference, however, is not statistically significant. The median duration of complete and partial remissions was slightly longer after treatment with melphalan than with adriamycin. The number of cycles required to produce the initial regression state was less in the patients in the group given adriamycin as compared with those in the group treated with melphalan. No cross resistance was observed between the two drugs. These data indicate that, in patients with carcinoma of the ovary, the therapeutic efficacy of adriamycin is competitive with that of the most effective conventional agents, such as melphalan.

Topics: Adenocarcinoma; Carcinoma; Clinical Trials as Topic; Doxorubicin; Drug Evaluation; Endometriosis; Female; Humans; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Melphalan; Neoplasm Metastasis; Ovarian Neoplasms; Remission, Spontaneous

Topics: Adolescent; Adult; Aged; Bone Marrow; Bone Neoplasms; Carcinoma; Child; Child, Preschool; Clinical Trials as Topic; Cyclophosphamide; Dactinomycin; Drug Synergism; Female; Fluorouracil; Gastrointestinal Neoplasms; Head and Neck Neoplasms; Humans; Lung Neoplasms; Male; Melanoma; Melphalan; Middle Aged; Mitomycins; Parotid Neoplasms; Sarcoma; Urogenital Neoplasms; Vincristine

Choroid plexus carcinoma (CPC) is a rare infantile brain tumor with an aggressive clinical course that often leaves children with debilitating side effects due to aggressive and toxic chemotherapies. Development of novel therapeutical strategies for this disease have been extremely limited owing to the rarity of the disease and the paucity of biologically relevant substrates. We conducted the first high-throughput screen (HTS) on a human patient-derived CPC cell line (Children Cancer Hospital Egypt, CCHE-45) and identified 427 top hits highlighting key molecular targets in CPC. Furthermore, a combination screen with a wide variety of targets revealed multiple synergistic combinations that may pave the way for novel therapeutical strategies against CPC. Based on in vitro efficiency, central nervous system (CNS) penetrance ability and feasible translational potential, two combinations using a DNA alkylating or topoisomerase inhibitors in combination with an ataxia telangiectasia mutated and rad3 (ATR) inhibitor (topotecan/elimusertib and melphalan/elimusertib respectively) were validated in vitro and in vivo. Pharmacokinetic assays established increased brain penetrance with intra-arterial (IA) delivery over intra-venous (IV) delivery and demonstrated a higher CNS penetrance for the combination melphalan/elimusertib. The mechanisms of synergistic activity for melphalan/elimusertib were assessed through transcriptome analyses and showed dysregulation of key oncogenic pathways (e.g. MYC, mammalian target of rapamycin mTOR, p53) and activation of critical biological processes (e.g. DNA repair, apoptosis, hypoxia, interferon gamma). Importantly, IA administration of melphalan combined with elimusertib led to a significant increase in survival in a CPC genetic mouse model. In conclusion, this study is, to the best of our knowledge, the first that identifies multiple promising combinatorial therapeutics for CPC and emphasizes the potential of IA delivery for the treatment of CPC.

Topics: Animals; Carcinoma; Child; Choroid Plexus Neoplasms; Humans; Mammals; Melphalan; Mice; Topotecan

Studies evaluating chemotherapy high dose chemotherapy with autologous haematopoietic stem cell transplantation (HDC-ACSH) in the treatment of metastatic (MBC), locally advanced (LABC) and inflammatory (IBC) breast cancer have in common lack of biomarker information, in particular the HER2 status.. All consecutive female patients treated for breast cancer with HDC and AHSCT at Institut Paoli Calmettes between 2003 and 2012 were included. Patients were categorized in three subtypes based on hormonal receptor (HR) and HER2 status of the primary tumor: luminal, (HR+/HER2-), HER2 (HER2+, any HR) and triple negative (TN) (HER2- and HR-). The main objective was the analysis of overall survival (OS) according to the IHC subtypes.. Three hundred and seventy-seven patients were included. For MBC, the TN subtype appeared to have the worst prognosis with a median OS of 19.68 months (95 % CI 11.76-44.4) compared to 44.64 months (95 % CI 40.32-67.56) for the luminal subtype and a median OS not reached for the HER2 subtype (P<0.01). For IBC, HER2 subgroup appeared to have the best prognosis with a 5-year OS of 89 % (95 % CI 64-97) compared to 57 % (95 % CI 33-76) for the TN subgroup (HR 5.38, 95 % CI 1.14-25.44; P=0.034). For CSLA, luminal subgroup appeared to have the best prognosis with a 5-year OS of 92 % (95 % CI 71-98) against 75 % (95 % CI 46-90) for HER 2 subtype and 70 % (95 %CI 97-88) for TN subtype (P=0.301).. The HDC-ACSH does not change the prognosis value of IHC subtype in breast cancer patients.

Topics: Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Autografts; Breast Neoplasms; Cancer Care Facilities; Carcinoma; Combined Modality Therapy; Cyclophosphamide; Female; Genes, BRCA1; Genes, BRCA2; Genes, erbB-2; Hematopoietic Stem Cell Transplantation; Humans; Melphalan; Middle Aged; Mitoxantrone; Prognosis; Retrospective Studies; Thiotepa

Cytoreductive surgery (CRS)/hyperthermic intraperitoneal chemotherapy (HIPEC) is the procedure of choice in patients with peritoneal dissemination from appendiceal cancer. Although recurrence rates are 26%-44% after first CRS/HIPEC, the role of repeated CRS/HIPEC has not been well defined. We hypothesize that patients undergoing multiple CRS/HIPEC's have meaningful long term survival.. A retrospective study of a prospective database of 294 patients with peritoneal carcinomatosis (PC) was conducted, of these 162 had PC of appendiceal origin. Twenty-six of these patients underwent 56 CRS/HIPEC. Survival and outcomes was analyzed.. The percentage of patients with pre-surgical PCI scores ≥ 20 for the first, second, and third CRS/HIPEC was 65, 65, and 25%, respectively. Complete cytoreduction (CC 0-1) at first, second, and, third surgeries was 96, 65 and 75%, respectively. The mean operating time was 10.1 h. There was no 30-day peri-operative mortality. Following the first, second, and third CRS/HIPEC 27, 42, and 50% experienced grade III complications, respectively. Mean follow up was 51, 28, and 16 months from the first, second, and third CRS/HIPEC, respectively. Overall survival rate for the first CRS/HIPEC was 100, 83, 54, and 46% at years 1, 3, 5 and 10, respectively; from the second CRS/HIPEC 91, 53, and 34% at 1, 3, and 5 years, respectively; and from the third CRS/HIPEC was 75% at one year.. Repeat CRS/HIPEC can lead to meaningful long term survival rates in patients with appendiceal peritoneal carcinomatosis with morbidity and mortality similar to those of the initial CRS/HIPEC.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Appendiceal Neoplasms; Carboplatin; Carcinoma; Chemotherapy, Adjuvant; Databases, Factual; Digestive System Surgical Procedures; Female; Humans; Hyperthermia, Induced; Infusions, Parenteral; Kaplan-Meier Estimate; Length of Stay; Male; Melphalan; Middle Aged; Mitomycin; Peritoneal Neoplasms; Reoperation; Retrospective Studies; Treatment Outcome

Late-stage ovarian carcinoma is almost universally fatal. BRCA mutations are associated with an improved outcome and enhanced sensitivity to platinum chemotherapy, yet recurrence and platinum resistance remain a major problem and highly effective regimens following platinum failure do not yet exist. Here we report a remarkable case of cure following platinum-resistant stage III ovarian carcinoma in a woman with a BRCA2 mutation. The patient was subsequently treated with oral melphalan therapy and has not recurred in over 25 years. Melphalan is a bifunctional alkylator that creates inter- and intra-strand DNA cross-links. In a pharmaceutical screen, melphalan was shown to be selectively toxic to BRCA2-deficient breast cancer cell lines and produced a longer relapse-free survival in mice than did cisplatin or olaparib. There is increasing evidence to consider BRCA mutation status when selecting chemotherapy regimens, and melphalan treatment for BRCA-related ovarian cancer merits further investigation. Focusing attention on long-term survivors may provide new mechanistic insights into the biology of chemo-responsiveness.

Topics: Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; BRCA2 Protein; Carcinoma; Chemotherapy, Adjuvant; Drug Resistance, Neoplasm; Female; Humans; Melphalan; Middle Aged; Neoplasm Staging; Ovarian Neoplasms; Time Factors; Treatment Outcome

Many patients with colorectal carcinoma develop unresectable metastases confined to the liver that remain the life-limiting component of disease despite best available systemic or regional chemotherapy. In the current study, the authors present their results using vascular isolation and perfusion of the liver for individuals with progressive, unresectable liver metastases from colorectal carcinoma that were refractory to both previous systemic and regional chemotherapy.. Seven patients with refractory, progressive, unresectable colorectal carcinoma metastases confined to the liver underwent a 60-minute hyperthermic (39-40 degrees C) isolated hepatic perfusion (IHP) and were followed for toxicity, response, and survival.. There was no surgical- or treatment-related mortality; all patients experienced transient Grade 3-4 (according to National Cancer Institute common toxicity criteria) hepatic toxicity. At a median potential follow-up of 16 months, the overall objective radiographic response rate (all partial responses) was 71% (5 of 7 assessable patients). It is interesting to note that two patients who were treated with tumor necrosis factor (TNF) alone demonstrated no response to therapy compared with all five patients who were treated with melphalan and TNF (three patients) or melphalan alone (two patients). For the 5 patients who responded to treatment, the median duration of response was 10 months (range, 10-13 months) and in all 7 patients the mean overall survival was 19.7 months (range, 2-33 months), including 5 months and 7.5 months, respectively, for the 2 patients treated with TNF alone.. The results of the current study demonstrate that IHP using melphalan with or without TNF has significant antitumor activity in this patient population. IHP deserves continued clinical evaluation as a therapeutic modality for patients with unresectable colorectal carcinoma metastases to the liver.

Topics: Aged; Antineoplastic Agents; Carcinoma; Chemotherapy, Cancer, Regional Perfusion; Cohort Studies; Colorectal Neoplasms; Drug Resistance, Neoplasm; Hepatic Veins; Humans; Liver Neoplasms; Male; Melphalan; Middle Aged; Tumor Necrosis Factor-alpha

to determine the outcome of epithelial ovarian cancer in patients registered with the European Group for Blood and Marrow Transplantation (EBMT).. A retrospective analysis was performed on 254 patients with advanced or recurrent disease, median age 46 years (14-63) from 39 centres treated between 1982 and 1996. Only 25% of patients were known to have no or microscopic disease after initial surgery; in approximately 20% the disease status was unknown, the remainder had macroscopic disease.. One hundred five patients received high-dose chemotherapy in complete or very good partial remission, twenty-seven in second remission and the remainder in the presence of residual disease. Most received melphalan or carboplatin, or a combination (86%) supported by autologous bone marrow or peripheral blood stem cells. The survival of patients treated in remission was significantly better than in other groups (median 33 vs. 14 months; P = 0.0001). The durability of remission was longer after transplantation in first remission than in second remission (median disease-free survival 18 vs. 9 months; P = 0.005). With a median follow-up of 76 months from diagnosis the median disease-free and overall survival in stage III disease transplanted in remission is 42 and 59 months and for stage IV disease 26 and 40 months.. High-dose chemotherapy has a potential benefit for patients in remission. The results support the conduct of randomised studies to determine whether there is a real value from this treatment.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Carboplatin; Carcinoma; Disease-Free Survival; Female; Follow-Up Studies; Humans; Melphalan; Middle Aged; Ovarian Neoplasms; Registries; Retrospective Studies

The theoretical advantage of regional vs. systemic chemotherapy was calculated, based on pharmacokinetic considerations. The relevance of exposure time and high local concentrations of chemotherapeutic drugs for regional chemotherapy was elucidated in time dependent concentration response curves with two human cell lines. The theoretical pharmacological advantage of regional vs. systemic chemotherapy was defined by the formula Rd = (AUCi. a. 1 + AUCi. a. 2)/(AUCi. v.) and in hepatic artery infusion is for adriamycin (ADM) 5.8-.6, cis-platinum (CDDP) 8, epirubicine (EPI) 6.3, 5-fluorouracil (5-FU) 22-58, mitomycin C (MMC) 4.6, mitoxantrone (NOV) 6.3. All drugs but 5-FUDR exerted concentration response behaviour in the cell line-experiments. In the cell lines cytotoxicity depended on exposure time so that concentration chi time products at (IC50), (c chi t (IC50)), were calculated to determine an optimal in vitro exposure time. Based on these results and clinical considerations, optimal clinical exposure times could be defined for regional chemotherapy. The results may be of high relevance for e.g. hepatic artery infusion at the lower and chemoembolization or intraperitoneal instillation at the higher test concentration, respectively.

Topics: Antibiotics, Antineoplastic; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Carcinoma; Cisplatin; Colorectal Neoplasms; Doxorubicin; Epirubicin; Floxuridine; Fluorouracil; Hepatic Artery; Humans; Infusions, Intra-Arterial; Melphalan; Mitomycin; Mitoxantrone; Tumor Cells, Cultured

Combination chemotherapy with hexamethylmelamine (hexalen, altretamine, hexastat), 100 mg, thrice a day, per os, 14 days (out of a 28-day course) and sarcolysin, 15 mg, per os, during the first 5 days of the course, was received by 24 patients with primary advanced tumors of the ovaries, prior to or after cytoreductive surgery. Total apparent response to chemotherapy among 19 patients of the study group was 47.2%, clinically significant (plus stabilization)--94.5%, without significant untoward side-effects (vomiting--19%; leukopenia degree II-III--33% and thrombocytopenia--19%). The drug proved an active component of combination therapy for advanced ovarian carcinoma.

Topics: Adult; Aged; Altretamine; Antineoplastic Agents, Alkylating; Carcinoma; Chemotherapy, Adjuvant; Drug Administration Schedule; Female; Humans; Melphalan; Middle Aged; Ovarian Neoplasms; Retrospective Studies; Treatment Outcome

A series of 53 patients with poor-prognosis epithelial ovarian cancer treated with high-dose chemotherapy (HDC) followed by hematopoietic rescue was retrospectively studied from the day of diagnosis for toxicity and long-term survival analysis.. Patients were treated with surgery followed by cisplatin combination chemotherapy. After second-look operation (SLO), HDC was administered: 23 patients received melphalan (140 mg/m2 on day 1) and 30 patients received a combination of carboplatin (400 mg/m2 on days 1 to 4) and cyclophosphamide (1.6 g/m2 on days 1 to 4). After HDC, autologous stem-cell transplantation was performed for hematologic support.. One patient died of cardiac failure after HDC, but the acute toxicity was acceptable for the other patients. With a median follow-up of 81.5 months, the 5-year overall survival rate for the 53 patients was 59.9% and the disease-free survival (DFS) rate at 5 years was 23.6%. Twenty-four patients (45.3%) were alive, 12 with no evidence of disease and 12 with recurrent disease. The best results were achieved in 19 patients with pathologic complete response at SLO (74.2% 5-year overall survival; 32.8% 5-year DFS).. HDC followed by autologous stem-cell support is a well-tolerated therapeutic approach for patients with poor-prognosis ovarian carcinoma. In this report, the 59.9% survival of 53 patients at 5 years must be compared to the 20% to 30% 5-year survival observed after conventional therapy. These results should be confirmed by an ongoing prospective randomized trial.

Topics: Adult; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma; Cyclophosphamide; Female; Hematopoietic Stem Cell Transplantation; Humans; Melphalan; Middle Aged; Neoplasm Staging; Ovarian Neoplasms; Prognosis; Retrospective Studies; Salvage Therapy; Survival Analysis; Treatment Outcome

Protein kinase C (PKC) has been implicated in propagating signals for apoptosis. We have investigated the effect of pharmacological modulation of PKC activity in DU-145 human androgen-independent prostatic carcinoma cells. The apoptotic death of these cells is characterized by the acquisition of classical apoptotic morphology and generation of > or = 1-mbp and 450- to 600-kbp DNA fragments in attached preapoptotic cell populations prior to cellular detachment and accrual of 30- to 50-kbp DNA fragments. We found that induction of apoptosis was arrested by downregulation of PKC activity and not by transient activation or inhibition of the enzyme. Concentrations and durations of exposure to phorbol esters that downregulated PKC activity correlated with inhibition of VP-16 or melphalan-induced morphological apoptosis and generation of the 30-to-50-kbp DNA fragments. Chronic exposure to phorbol-12,13-dibutyrate (PDBu) did not, however, suppress production of the > or = 1-mbp and 450- to 600-kbp DNA fragments found in preapoptotic cell populations, suggesting that PKC downregulation may interfere with the transition between a preapoptotic cell and an apoptotic cell. PKC isozyme analysis revealed that chronic PDBu treatment caused downregulation of PKC-alpha and -epsilon in DU-145 cells. Using concentrations of the PKC inhibitor UCN-01 that were consistent with PKC-alpha inhibition (but not PKC-epsilon inhibition), however, did not mimic the effects of chronic PDBu treatment, implying that downregulation of PKC-epsilon may be of particular importance. Together, these findings suggest that phorbol esters may act as tumor promoters by suppressing apoptosis.

Topics: Antineoplastic Agents; Apoptosis; Carcinogens; Carcinoma; Cell Adhesion; Down-Regulation; Enzyme Activation; Etoposide; Gene Expression Regulation, Neoplastic; Humans; Male; Melphalan; Phorbol Esters; Prostatic Neoplasms; Protein Kinase C; Tumor Cells, Cultured

The sensitivity of tumor cells to lysis by natural killer (NK) and interleukin-2 (IL-2)-activated killer (LAK) cells was studied in three ovarian carcinoma cell lines (2780.9S, SKOV-3, and CHOAUXB1), four multidrug-resistant (MDR) variants, and a melphalan-resistant line. The antitumor activity of LAK cells was evaluated both by 51Cr release and by conjugate formation assays. Four of four P-glycoprotein-positive (P-gp+) MDR ovarian carcinoma cell line variants were lysed by human LAK cells to a greater extent than were their drug-sensitive counterparts. In contrast, a melphalan-resistant ovarian carcinoma cell line that does not overexpress P-gp (P-gp-) did not exhibit an increased susceptibility to LAK cells relative to its parental cell line. Two of the four P-gp+ MDR ovarian carcinoma cell line variants were tested for human NK cell susceptibility and this was found to be unchanged or decreased. The P-gp+ MDR ovarian carcinoma cell line 2780.AD645 showed a higher frequency of tumor cell binding to LAK cells than did the drug-sensitive parental line. A monoclonal antibody (mAb) against a cell surface epitope of P-gp, MRK16, used at 1 microgram/ml, enhanced the LAK susceptibility of P-gp+ MDR ovarian carcinoma cell lines. However, when incubation with 10 micrograms/ml MRK-16 antibody (Ab) was followed by 12.5 micrograms/ml F(ab')2 goat anti-mouse (GAM) immunoglobulin (Ig), the increased LAK susceptibility of P-gp+ MDR cell lines was inhibited. These data strongly suggest that P-glycoprotein-positive MDR ovarian carcinoma cells not only are targets for LAK cells, but are more sensitive than their drug-sensitive parental lines. This is in contrast to their susceptibility to NK cells, which is low to start with and remains unchanged or even decreased in MDR cells. It is postulated here that P-gp or associated changes result in a greater frequency of effector-target cell binding, leading to increased LAK cell cytotoxicity.

Topics: Animals; Antibodies, Monoclonal; Antineoplastic Agents, Alkylating; ATP Binding Cassette Transporter, Subfamily B, Member 1; Carcinoma; CHO Cells; Cricetinae; Cytotoxicity, Immunologic; Drug Resistance, Multiple; Female; Humans; Interleukin-2; Killer Cells, Lymphokine-Activated; Killer Cells, Natural; Melphalan; Ovarian Neoplasms; Tumor Cells, Cultured

Topics: Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Carcinogens; Carcinoma; Combined Modality Therapy; Cyclophosphamide; Ethmoid Sinus; Female; Fluorouracil; Follow-Up Studies; Humans; Leiomyosarcoma; Mastectomy, Modified Radical; Melphalan; Methotrexate; Neoplasms, Second Primary; Paranasal Sinus Neoplasms

Recombinant tumor necrosis factor alpha (rTNF alpha) has potent antitumor activity in experimental studies on human tumor xenografts. However, in humans, the administration of rTNF alpha is hampered by severe systemic side effects. The maximum tolerated dose ranges from 350 to 500 mg/m2, which is at least 10-fold less than the effective dose in animals. Isolated perfusion of the limbs (ILP) allows the delivery of high-dose rTNF alpha in a closed system with acceptable side effects. A protocol with a triple-drug regimen was based on the reported synergism of rTNF alpha with chemotherapy, with interferon-gamma, and with hyperthermia. In patients with melanoma-in-transit metastases (stage IIIA or AB), we obtained a 91% complete response rate compared with 52% after ILP with melphalan alone. In unresectable soft tissue sarcomas, this protocol was found to produce a 50% complete response with 87.5% limb salvage, since most tumors became removable. Release of nanograms levels of TNF alpha in the systemic circulation was evident, but control of this leakage and appropriate intensive care resulted in acceptable toxicity. Angiographic, immunohistological, and immunological studies suggest that the efficacy of this protocol is due to a dual targeting: rTNF alpha activates and electively lyses the tumor endothelial cells, while melphalan is mainly cytotoxic to the tumor cells. ILP with rTNF alpha appears to be a useful model for studying the biochemotherapy of cancer in man.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Chemotherapy, Cancer, Regional Perfusion; Clinical Protocols; Dose-Response Relationship, Drug; Extremities; Humans; Interferon-gamma; Melanoma; Melphalan; Pilot Projects; Recombinant Proteins; Sarcoma; Soft Tissue Neoplasms; Treatment Outcome; Tumor Necrosis Factor-alpha

The incidence of ovarian cancer has been increasing gradually over the last 25 years. The presenting symptoms are non-specific and, in many cases, there is extensive intraabdominal spread at the time of diagnosis. Diagnosis is based on abdominal ultrasonography followed by laparotomy for tumor classification and extensive excision. Assay of CA125 can be a useful diagnostic tool for post-menopausal women, and for determining the response to treatment. Routine screening for ovarian cancer is not feasible. The most important prognostic factor is tumor extension. In early stages, chemotherapy does not improve the prognosis in "low-risk" patients, and its value in high-risk patients remains to be determined. In patients with advanced-stage ovarian carcinoma, platinum derivatives are the reference drugs. The high toxicity of cisplatin has led to the development of carboplatin, which has similar activity but virtually no nephrotoxicity, neurotoxicity or ototoxicity. Carboplatin is currently considered as the cytostatic drug of choice, as it can be given at higher doses which may improve the survival time. The possible indications for intraperitoneal chemotherapy remain to be determined. Secondary laparotomy should not be used, except in clinical trials. Taxol (paclitaxel), a new cytostatic agent that prevents mitosis through an original mode of action, is currently undergoing evaluation.

Topics: Antigens, Tumor-Associated, Carbohydrate; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma; Cisplatin; Female; Humans; Injections, Intraperitoneal; Melphalan; Neoplasm Staging; Ovarian Neoplasms; Paclitaxel; Prognosis; Risk Factors; Survival Analysis

We have derived sublines of three human lung cancer cell lines with acquired resistance to cisplatin. The cisplatin resistant sublines of NCI-H69 (small cell), COR-L23 (large cell), and MOR (adenocarcinoma) show 5.3 fold, 3.1 fold, and 3.8 fold resistance, respectively, determined in a 6-day MTT assay. Although the parent lines show a wide range of glutathione content per cell, the sublines each show similar values to their corresponding parent line. Radiation response curves have been obtained using a soft agar clonogenic assay. Values obtained for the parent lines (95% CL in parentheses) were: NCI-H69: Do = 0.99 Gy (0.87-1.16), n = 2.9 (1.6-5.2), GSH = 14 ng/10(4) cells; COR-L23: Do = 1.23 Gy (1.05-1.49), n = 1.3 (0.7-2.2), GSH = 47 ng/10(4) cells; MOR: Do = 1.66 Gy (1.48-1.88), n = 3.0 (1.9-4.8), GSH = 86 ng/10(4) cells. The cisplatin resistant variants of NCI-H69 and COR-L23 showed 31% and 63% increases, respectively, in Do compared to their parent lines, whereas no change in radiation response was seen in MOR. In this panel of lines, therefore, although there is a correlation between glutathione content and radiosensitivity of the parent cell lines, acquired resistance to cisplatin is not accompanied by increased glutathione content. However, two of the three cisplatin resistant lines do show a significantly reduced radiosensitivity.

Topics: Adenocarcinoma; Carcinoma; Carcinoma, Small Cell; Cisplatin; Dose-Response Relationship, Radiation; Drug Resistance; Glutathione; Glutathione Transferase; Humans; Lung Neoplasms; Melphalan; Radiation Tolerance; Tumor Cells, Cultured

Topics: Adult; Carcinoma; Combined Modality Therapy; Female; Humans; Melphalan; Ovarian Neoplasms

The two monoclonal antibodies (mAb), L6 (anti-carcinoma), and 1F5 [anti-(B-cell-lymphoma)], were chemically linked to the enzyme penicillin-V amidase (PVA), which hydrolyzes phenoxyacetamides, to explore the potential of using mAb-enzyme conjugates for the localization of chemotherapeutic drugs at tumor cells. The phenoxyacetamide derivatives of doxorubicin and melphalan were prepared, yielding the less toxic amides, doxorubicin-N-p-hydroxyphenoxyacetamide (DPO) and melphalan-N-p-hydroxyphenoxyacetamide (MelPO). These were hydrolyzed by PVA to doxorubicin and melphalan respectively. In vitro studies with the L6-positive lung carcinoma cell line, H2981, and the 1F5-positive B-cell lymphoma line, Daudi, showed that DPO was 80-fold less toxic to H2981 cells and 20-fold less toxic to Daudi cells than doxorubicin, and its toxicity was substantially increased when the H2981 cells were pretreated with L6-PVA or the Daudi cells were pretreated with 1F5-PVA. The cytotoxic effect was antigen-specific, since only the binding mAb-enzyme conjugate increased the cytotoxicity of the prodrug. MelPO was more than 1000-fold less toxic than melphalan to H2981 cells and more than 100-fold less toxic than melphalan to Daudi cells. Pretreatment with the mAb-PVA conjugates did not enhance the toxicity of MelPO in either cell line, because PVA hydrolyzes the phenoxyacetamide bond of MelPO too slowly to generate a toxic level of melphalan.

Topics: Amidohydrolases; Antibodies, Monoclonal; Antigens, Neoplasm; Carcinoma; Doxorubicin; Humans; Immunotoxins; Lymphoma; Melphalan; Penicillin Amidase; Penicillin V; Prodrugs; Tumor Cells, Cultured

We retrospectively evaluated the feasibility and antitumour efficacy of high dose melphalan (HDM) followed by autologous marrow rescue in 35 patients with common epithelial ovarian cancers. All patients initially had advanced disease (FIGO III-IV) and received HDM after extensive surgery and a median of 6 cycles of cis-DDP containing regimens CAP or CHAP. All, except three patients who showed evidence of progression, had a second surgical exploration before high dose chemotherapy. Melphalan was given at a dosage greater than or equal to 140 mg/m2 followed 24 h later by autologous marrow rescue. Severe but reversible aplasia and mucositis were the most common toxicities: three patients died from the procedure, two from infection and one from secondary leukaemia. HDM was effective in 75% of evaluable patients; this was evidence of activity in patients who failed to respond to first line chemotherapy. The duration of response was short, particularly for patients treated with progressive disease at the time of high dose chemotherapy rather than in partial or complete remission. With a median follow-up of 23 months (range 8-54) after high dose chemotherapy, 19 patients are alive (15 with non-progressive disease) with a projected survival of 47% between 2 and 5 years.

Topics: Adult; Bone Marrow Transplantation; Carcinoma; Dose-Response Relationship, Drug; Female; France; Humans; Melphalan; Middle Aged; Ovarian Neoplasms; Prognosis; Retrospective Studies; Transplantation, Autologous

Patients with epithelial ovarian carcinoma (OVCA) and positive second-look operation (SLO) have a poor short-term prognosis. Treatment after SLO is still controversial and pilot studies are justified in an attempt to improve survival of these patients. As OVCA is known to be a chemosensitive tumor, it seems logical to treat these patients with high-dose chemotherapy with the support of an autologous bone marrow transplantation. Fourteen patients underwent primary surgery with tumor debulking followed by cis-platinum-based chemotherapy. SLO was performed in each patient and was microscopically positive in five and macroscopically positive with secondary debulking in nine. All patients were treated after SLO with high-dose melphalan (HDM), 140 mg/m2, and autologous bone marrow support. HDM was well tolerated, with a median time to granulocyte recovery of 21 days. There was no death due to treatment toxicity. The mean follow-up after SLO is 43 months. Five patients (35.7%) are disease free at 30 to 60 months after SLO with no further treatment and, thus, a good quality of life. Four patients are alive with recurrent disease. Five patients died of OVCA; actuarial 3-year survival is 64%. This therapeutic procedure is well tolerated and seems to provide long-term survival for patients with no complete response after first-line chemotherapy. Therefore, it might also be applied to patients at high risk of recurrence after a negative SLO.

Topics: Adenocarcinoma; Adult; Bone Marrow Transplantation; Carcinoma; Combined Modality Therapy; Female; Follow-Up Studies; Hematopoiesis; Humans; Melphalan; Middle Aged; Neoplasm Recurrence, Local; Ovarian Neoplasms; Pilot Projects; Reoperation

Forty-one patients with epithelial ovarian tumors of low malignant potential are discussed. Twenty-three patients presented with Stage I, four with Stage II and 14 with Stage III disease. All patients with Stage I disease were solely treated surgically. Twelve patients with Stage II and III disease also received postoperative chemotherapy. Four of ten patients had persistent disease at second look laparotomy. Chemotherapy was not used in six patients with Stage II and III disease when the tumor was considered to have been removed completely. Forty of the 41 patients are currently alive and free of disease at two to nine years of follow-up study. Vigorous and, at times, multiple surgical procedures remain the primary treatment of ovarian tumors of low malignant potential.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Cyclophosphamide; Doxorubicin; Female; Humans; Melphalan; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Ovarian Neoplasms; Peptichemio; Reoperation; Retrospective Studies

In vivo mutations at the locus for hypoxanthine phosphoribosyl transferase (hprt) were studied in 6-thioguanine (TG)-resistant T-lymphocyte clones from healthy male and female subjects and ovarian carcinoma patients treated with melphalan. Southern blot analysis of 108 clones showed alterations in 14% (4/29) of the clones from healthy males, 4.3% (2/47) of the clones from healthy females and 3.1% (1/32) of the clones from melphalan-treated patients. 2 of the 7 abnormal clones had a total deletion of the hprt gene; the others had partial deletions. Karyotype analysis of 82 clones revealed 1 clonal abnormality in 29 mutant clones from healthy males (3.6%). Loss or structural aberration of 1 X-chromosome occurred in 6% of the clones from healthy females. The frequency of karyotypic abnormalities (excluding those affecting one of the X-chromosomes) was significantly higher in clones from patients (37%) as compared to healthy females (5.9%). No aberration was found to affect the hprt locus at Xq27 in any of the 82 clones studied.

Topics: Blotting, Southern; Carcinoma; Chromosome Aberrations; Chromosome Disorders; Clone Cells; Female; Humans; Hypoxanthine Phosphoribosyltransferase; Karyotyping; Melphalan; Mutation; Ovarian Neoplasms; T-Lymphocytes

Melphalan (MEL), an alkylating agent, has been modified to a derivative, N-acetylmelphalan (N-AcMEL), which can be conjugated to anticolon cancer monoclonal antibodies (MoAbs 30.6, I-1, and JGT) and used for immunochemotherapy. The final immunoconjugates possess potent cytotoxicity and specificity in preclinical studies. In a phase I clinical study, N-AcMEL-MoAb conjugates were administered via the hepatic artery to 10 patients, nine of whom had disseminated colorectal cancer (including the liver) and one of whom had Dukes' C colon cancer that had been resected. The selection of MoAb was based on the immunoperoxidase staining of the primary colon cancer tissue. Thus far doses of 1000 mg/m2 MoAb conjugated to 20 mg/m2 of N-AcMEL have been administered with no significant side effects, whereas MEL unconjugated to monoclonal antibodies would have caused myelosuppression in a proportion of patients at the same dosage. Serum antimouse antibody responses were noted in all of the patients; febrile reactions were noted with higher doses but were easily controlled with antipyretics, antihistamines and, if necessary, steroids. Serum sickness developed in one patient who was given a second course of treatment in the presence of human antimouse antibody, but the episode was self-limiting. Eight of the 10 patients had evaluable disease. Subjective improvement was noted in almost all of the patients examined, and 33%, or 3 of 9, of the treatments (nine courses of treatment in eight patients with evaluable disease; one of the patients had two courses of treatment) led to antitumor responses (minor response) by objective assessment with computed tomography of the liver. It is important to note that treatment with N-AcMEL-MoAb conjugates was safe at a dose of 20 mg/m2 of N-AcMEL, whereas the efficacy of such a form of treatment remains to be determined.

Topics: Adult; Antibodies, Monoclonal; Antineoplastic Agents; Carcinoembryonic Antigen; Carcinoma; Colorectal Neoplasms; Drug Evaluation; Female; Humans; Immunohistochemistry; Immunotoxins; Male; Melphalan; Middle Aged; Neoplasm Metastasis; Tomography, X-Ray Computed

Twenty-nine patients were treated with 31 courses of high-dose combination cyclophosphamide, cisplatin, and carmustine (BCNU) with and without melphalan with autologous bone marrow support. Toxicity was dose related. The maximum tolerated dose for cyclophosphamide, cisplatin, and BCNU in this combination in mg/m2 was 5,625, 165, and 600, respectively. Further dose escalation was precluded by the development of multiple organ toxicity, including venoocclusive disease, refractory thrombocytopenia, and hypertension. Melphalan added to the three-drug combination produced excessive renal and gastrointestinal toxicity. Objective tumor regression occurred in 21 of 25 evaluable cases. The results suggest that selected alkylating agents can be combined in full or nearly full doses before nonmyelosuppressive dose-limiting toxicity precludes further escalation.

Topics: Adult; Alkylating Agents; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Carcinoma; Carmustine; Cisplatin; Cyclophosphamide; Dose-Response Relationship, Drug; Drug Evaluation; Drug Tolerance; Female; Humans; Male; Melphalan; Middle Aged; Neoplasm Metastasis; Sarcoma

Cytogenetic studies were carried out on peripheral lymphocytes from cancer patients at different times after therapy with melphalan. The frequency of sister chromatid exchange (SCE) was increased markedly shortly after treatment, and then declined to near pretreatment levels over a four-week period. In-vitro studies showed that the SCE frequency induced by melphalan is reduced slowly in resting G0 lymphocytes and considerably faster in mitogen-stimulated G1 cells. The results demonstrate that measurement of SCE is useful for the study of newly-induced chromosome damage in melphalan-treated cells, but is less suitable for the detection of persistent, cytogenetic alterations long after therapy. The frequency of chromosomal aberrations in a cohort of 50 patients with ovarian carcinoma was increased for up to ten years after melphalan therapy. The predominant aberrations were chromosomal translocations, marker chromosomes and cells with multiple, complex rearrangements. The frequency distribution of chromosomes involved in aberrations was studied in cells from some of the patients. An overrepresentation of chromosomes 8 and 9 was found in these cells, whereas the X chromosome was overrepresented in cells from control subjects. An increased frequency of chromosomal rearrangements was found in long-term cultures of T-lymphocytes from three of the patients, indicating that these aberrations are compatible with cell survival and proliferation. Seven patients in the cohort developed a second, primary tumour during the observation time. The frequencies and types of aberrations in these patients were similar to those of the other patients in the cohort.

Topics: Carcinoma; Cell Division; Cell Survival; Chromosome Aberrations; Chromosomes; DNA Damage; Female; Humans; In Vitro Techniques; Karyotyping; Lymphocytes; Melanoma; Melphalan; Neoplasms; Ovarian Neoplasms; Sister Chromatid Exchange; Thrombocytopenia; Time Factors

We investigated the synergistic anti-tumor effects of K-18 (conjugate of human gamma-globulin and melphalan) and concomitantly administered hyperthermia on Lewis lung carcinoma in mice. The antitumor effect of a subeffective dose of K-18 or an equivalent dose of melphalan alone was enhanced by local hyperthermia. K-18 administration demonstrated a greater potentiation for inhibition of tumor growth than that of melphalan alone. Local hyperthermia plus K-18 reduced the dose of melphalan required for tumor growth inhibition by melphalan alone. The combined application of K-18 and hyperthermia for treating cancer warrants further study.

Topics: Animals; Carcinoma; Combined Modality Therapy; Drug Combinations; Female; gamma-Globulins; Humans; Hyperthermia, Induced; Immunotoxins; Lung Neoplasms; Melphalan; Mice; Tissue Distribution

From 1980 to 1984 fifty-four patients with advanced ovarian carcinoma after operation and concluding chemotherapy with alkeran (n = 7) or cis-platin/alkeran +/- hexamethylmelamine (n = 47) as well as second-look laparotomy received follow-up radiotherapy either with the moving-strip technique (n = 35) or later the open-field technique (n = 19). 32 patients in CR received radiation therapy. 15 patients in CR are without relapse after undergoing open-field radiation therapy and a mean observation period of 25 months. At this point of time 5 of 17 patients had relapses under the moving-strip radiation treatment. The frequency of the relapses is apparently due to the very long periods of radiation and numerous interruptions in treatment. If residual tumors were present at the begin of ray therapy, a CR could only be achieved in cases where the previous monotherapy was with alkeran.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Cisplatin; Combined Modality Therapy; Endometriosis; Female; Humans; Melphalan; Middle Aged; Ovarian Neoplasms; Prognosis; Reoperation

From January 1978 to October 1982, 47 patients with histological diagnosis of epithelial cancer of the ovary received peptichemio (PTC) at a dose of 70 mg/m2 (maximum, 120 mg total) every 15 days. Forty-two patients are now evaluable: 27 with stage III and 15 with stage IV disease. All patients but four with stage IV disease had been pretreated and had received at least one drug combination (median, three drugs per patient, including alkylating agents). Before the administration of PTC, the tumor extension in the abdomen was carefully assessed in all patients: ten patients had residual tumor less than 2 cm in diameter, while 32 patients had tumor greater than 2 cm in diameter. Objective responses were obtained in ten patients (23.8%): six complete remissions and one partial remission were observed in stage III patients and one complete remission and two partial remissions were observed in stage IV patients. Of the ten responding patients, eight had tumors less than 2 cm in diameter before receiving PTC. The median duration of response was 16 months. The most frequent side effects were myelosuppression and phlebosclerosis. Bone marrow depression was a common finding after the third course in heavily pretreated patients. Accordingly, in these patients a schedule interval of 3 weeks should be more appropriate. Since most of the responders were in the "small tumor" category, PTC appears to be an active drug in patients with ovarian cancer having small tumors (less than 2 cm). On the other hand, the response rate in a nonselected population of patients remains to be clearly defined with further studies.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Carcinoma; Drug Eruptions; Female; Humans; Leukocyte Count; Melphalan; Middle Aged; Nausea; Ovarian Neoplasms; Peptichemio; Platelet Count; Vomiting

Open-field gamma-beam therapy using grid filters was used for 53 patients with Stage III-III stomatopharyngeal tumors. Besides, to compare therapeutic efficacy the 2nd group was taken (52 persons with Stage III-IV) where chemotherapy was used simultaneously. Single and summary radiation doses did not lower. A chemotherapeutic agent dose was equal to 1/2 up to 2/3 of the standard one. Powerful substitution and hemostimulation therapy and a great variety of drugs were employed not to induce deep changes of hemopoiesis and immunosuppression. A single focal dose in gamma-beam therapy varied from 1.6 to 2.5 Gy, the summary dose from 55 to 70 Gy depending on the stage of disease and the histological structure of a tumor. The prescription of one or another chemotherapeutic agent was mainly determined by the morphological structure of a tumor.

Topics: Adult; Aged; Carcinoma; Combined Modality Therapy; Cyclophosphamide; Gamma Rays; Humans; Melphalan; Methotrexate; Middle Aged; Oropharyngeal Neoplasms; Pharyngeal Neoplasms; Prognosis; Sarcoma; Thiotepa

Seventy-one cases of primary adenocarcinoma of the fallopian tube treated at The University of Texas M. D. Anderson Hospital and Tumor Institute at Houston were reviewed. The most common presenting symptoms were abdominal pain, abnormal uterine bleeding, and vaginal discharge. The most common physical finding was a palpable abdominal or pelvic mass. The preoperative diagnosis was correct for two patients. Initial therapy consisted of surgery alone, surgery plus radiation therapy, surgery plus chemotherapy, and a combination of surgery, chemotherapy, and radiation therapy in 10, 32, 21, and eight cases, respectively. The median survival for patients in these treatment groups was 33, 22, 27, and 22 months, respectively; the median survival for all patients was 23 months. No statistically significant differences emerged among the survival curves of patients treated with each of the above regimens.

Topics: Adenocarcinoma; Adenocarcinoma, Papillary; Adult; Aged; Alkylating Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Cisplatin; Combined Modality Therapy; Fallopian Tube Neoplasms; Female; Humans; Melphalan; Middle Aged; Progestins; Time Factors

Topics: Carcinoma; Female; Humans; Immunotherapy; Interferons; Melphalan; Ovarian Neoplasms; Propionibacterium acnes

Between 1970 and 1980, 50 patients with carcinoma of the ovary were treated sequentially with six courses of IV phenylalanine mustard (L-PAM), second look surgery, and radiotherapy using the strip technique. Seven patients had advanced Stage I disease and six patients had Stage II disease; all of these patients are alive and well with no evidence of disease (NED) with a mean survival of five years. Thirty-seven patients had Stage III disease: ten of these patients did not respond to L-PAM (26%); 17 patients had a partial response (48%), and four of these (22%) are alive with NED and a mean survival of five years; ten patients (26%) had a complete response to L-PAM and all are alive and well with a mean survival of five years. The presence of a minimal tumor burden after the initial surgery, a mixed histology, a low-grade differentiation, suppression of leukocyte count to below 2000/mm3 after the first course of chemotherapy, and a complete response to L-PAM, were all factors that contributed to the probability of a long-term survival. Tumors responding to L-PAM and then recurring also responded to a combination of cisplatin and adriamycin, and hexamethylmelamine.

Topics: Adult; Aged; Carcinoma; Female; Humans; Melphalan; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Ovarian Neoplasms; Prognosis; Radiotherapy, High-Energy; Time Factors

Between 1958 and 1973, 2412 women with epithelial ovarian carcinoma were treated at Radiumhemmet. Of these tumors, 14.5 per cent were of borderline malignancy. The 5-year relative survival rate was 34 per cent among the patients with true malignant tumor and 93 per cent in the borderline cases. Even in advanced stages (IIb-IV) the 5-year survival rate was 78 per cent in the borderline cases. Advanced stage and high age at diagnosis, true malignancy and tumors of serous, clear cell or anaplastic type were associated with poor prognosis. The 5-year relative survival rate of patients with epithelial ovarian carcinoma in an early stage improved during the period, from 67 to 81 per cent.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Carcinoma; Endometriosis; Female; Follow-Up Studies; Humans; Melphalan; Middle Aged; Ovarian Neoplasms; Prognosis; Radiotherapy Dosage; Statistics as Topic; Time Factors

Following surgery for epithelial carcinoma of the ovary, FIGO stages IIc, III and IV, 110 patients received chemotherapy in one of four treatment regimens (Melphalan; Cyclophosphamide-Methotrexate-Fluoro uracil; Cyclophosphamide-Cisplatinum; Cyclophosphamide-Cisplatinum-Fluoro-uracil). Melphalan alone was as effective as combination chemotherapy and less toxic. The study confirms that the survival duration is inversely correlated to the stage of the disease and to the amount of residual disease following surgery. It also confirms the role of the "second look" surgery in the evaluation of the response to chemotherapy, and in the overall management of the disease.

Topics: Adult; Aged; Antineoplastic Agents; Carcinoma; Cisplatin; Cyclophosphamide; Drug Therapy, Combination; Female; Fluorouracil; Follow-Up Studies; Humans; Laparotomy; Melphalan; Methotrexate; Middle Aged; Neoplasm Staging; Ovarian Neoplasms

Fifteen patients with clinical primary inflammatory carcinoma of the breast were treated with initial chemoimmunotherapy between September 1974 and May 1977. The protocol was a combination of Adriamycin, vincristine, 5-fluorouracil, and methotrexate given by I.V. push, and melphalan per os. Thermographic cooling was taken as the criterion of operability. Initial chemotherapy was resumed after surgery up to a total of ten courses and followed by maintenance chemotherapy for a minimum of one year. Immunotherapy using I-BCG-F. Pasteur was routinely associated with the antimitotic agents. The median survival for our 15 patients has not been reached and exceeds 56 months. These results correspond to an obvious therapeutic benefit compared with recent attempts in which similar chemoimmunotherapy protocols were used; this benefit seems to be the consequence of the adaptation of the length of initial chemotherapy to the data given by plate-thermography.

Topics: Aged; Antineoplastic Agents; BCG Vaccine; Breast Neoplasms; Carcinoma; Doxorubicin; Drug Evaluation; Drug Therapy, Combination; Fluorouracil; Humans; Melphalan; Methotrexate; Middle Aged; Thermography; Time Factors; Vincristine

The present work uses an in vitro test model to measure the sensitivity of human ovarian cancer cells to Melphalan and Melphalan combined with Adriamycin. With this model we studied the possible correlation between the in vitro results and the response to these cytostatic drugs in vivo. Cancer cells from 20 patients with advanced ovarian cancer were tested. The in vitro effects of the drugs were measured as differences in incorporation of labeled 3H-thymidine in drug containing tubes and in control tubes. The effects of the drugs on the different cancer cells varied greatly from strong sensitivity to resistance. In vitro and in vivo results were compared one year after start of patient treatment. The overall agreement was 16/20, 80%. The in vitro method thus estimates a tumor cell characteristic which has a biological meaning also in in vivo conditions.

Topics: Adenocarcinoma; Carcinoma; Cells, Cultured; Doxorubicin; Drug Evaluation, Preclinical; Drug Therapy, Combination; Endometriosis; Female; Humans; In Vitro Techniques; Melphalan; Ovarian Neoplasms; Retrospective Studies

The susceptibility of tumor tissue to therapeutic and smaller doses of chemotherapeutic drugs was assessed on the basis of SH-group inhibition in vitro. As therapeutic dose was decreased, rhythmic changes of tumor susceptibility were observed. In the experiments on tumor-bearing rats, the small dose of chemotherapeutic agent, which in preliminary in vitro experiments proved to be as effective as therapeutic one (1/5 therapeutic dose), was found to cause the same suppression of tumor growth. However, it did not induce leukopenia, lymphopenia, thymus involution or any other manifestations of stress which followed multiple injections of therapeutic doses. The white blood cell and thymus indices in rats, which received the small dose, suggest the development of reactions of training and activation which increase the nonspecific resistance of organism.

Topics: Adaptation, Physiological; Animals; Antineoplastic Agents; Carcinoma; Cyclophosphamide; Drug Resistance; In Vitro Techniques; Male; Melphalan; Neoplasms, Experimental; Rats; Sarcoma, Experimental; Thiotepa

Fibrinogen/fibrin degradation products (FDP) in the serum of 50 patients with ovarian carcinoma was examined by Nyléhn's immunochemical method. FDP were rarely found in early but frequently in advanced stages of ovarian tumours. With successful treatment, FDP decreased; otherwise persistently high FDP concentrations were observed in the serum. The determination serum FDP might be a valuable aid in assessing the effect of treatment.

Topics: Adult; Aged; Carcinoma; Cyclophosphamide; Cystadenocarcinoma; Female; Fibrin Fibrinogen Degradation Products; Fluorescent Antibody Technique; Humans; Melphalan; Middle Aged; Ovarian Neoplasms

Topics: Adult; Aged; Carcinoma; Humans; Male; Melphalan; Middle Aged; Pilot Projects; Prostatic Neoplasms; Time Factors

Topics: Adenocarcinoma; Adult; Aged; Carcinoma; Carcinoma, Squamous Cell; Chemotherapy, Cancer, Regional Perfusion; Female; Humans; Male; Melphalan; Middle Aged; Parotid Neoplasms; Remission, Spontaneous; Thiotepa

Topics: Carcinoma; Chemotherapy, Cancer, Regional Perfusion; Extremities; Humans; Melanoma; Melphalan; Neoplasms; Osteosarcoma; Skin Neoplasms; Thiotepa

Topics: Alkylating Agents; Animals; Carcinoma; Carcinoma, Brown-Pearce; Cyclophosphamide; Male; Melphalan; Neoplasms, Experimental; Nitrogen Mustard Compounds; Rats; Sarcoma, Experimental; Sulfhydryl Compounds

Topics: Carcinoma; Cecal Neoplasms; Cobalt Isotopes; Female; Fibrosarcoma; Humans; Kidney Neoplasms; Lymphoma, Large B-Cell, Diffuse; Male; Maxillary Neoplasms; Melanoma; Melphalan; Multiple Myeloma; Myxosarcoma; Palliative Care; Radioisotope Teletherapy; Testicular Neoplasms

Topics: Antimetabolites; Antineoplastic Agents; Breast Neoplasms; Carcinoma; Chlorambucil; Choriocarcinoma; Cyclophosphamide; Female; Fluorouracil; Hodgkin Disease; Humans; Hydrazines; Intestinal Neoplasms; Melphalan; Methotrexate; Multiple Myeloma; Ovarian Neoplasms; Pregnancy; Thiotepa; Vinblastine

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Antineoplastic Agents; Carcinoma; Cystadenocarcinoma; Cystadenoma; Endometriosis; Female; Humans; Melphalan; Middle Aged; Ovarian Neoplasms

Topics: Adenocarcinoma; Ameloblastoma; Antineoplastic Agents; Astrocytoma; Brain Neoplasms; Carcinoma; Carcinoma, Squamous Cell; Cyclophosphamide; Ethylenediamines; Facial Neoplasms; Fibrosarcoma; Glioma; Humans; Infusions, Parenteral; Mechlorethamine; Melanoma; Melphalan; Meningioma; Methotrexate; Osteosarcoma; Perfusion; Quinones; Retinoblastoma; Rhabdomyosarcoma; Sarcoma; Thiotepa

Topics: Antineoplastic Agents; Carcinoma; Chemotherapy, Cancer, Regional Perfusion; Fluorouracil; Head; Head and Neck Neoplasms; Humans; Leucovorin; Melanoma; Melphalan; Methotrexate; Mouth Neoplasms; Nasopharyngeal Neoplasms; Paranasal Sinus Neoplasms; Sarcoma; Thiotepa; Vinblastine

Topics: Alkylating Agents; Antineoplastic Agents; Carcinogens; Carcinoma; Chlorambucil; Cyclophosphamide; Dogs; Melphalan; Methotrexate; Naphthalenes; Neoplasms; Neoplasms, Experimental; Nitrogen Mustard Compounds; Pharmacology; Research; Toxicology; Urinary Bladder Neoplasms

Topics: Amines; Animals; Antimetabolites; Ascites; Carcinoma; Carcinoma, Ehrlich Tumor; Gallic Acid; Hydrolyzable Tannins; Melphalan; Pharmacology; Protein Biosynthesis; Proteins; Research; Thiotepa

Topics: Animals; Carcinoma; Carcinoma 256, Walker; Dipeptides; Melphalan; Mice; Nitrogen Mustard Compounds; Pharmacology; Rats; Research; Sarcoma, Experimental

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Carcinoma; Drug Therapy; Humans; Kidney Neoplasms; Kidney Pelvis; Melphalan; Neoplasms; Nephrectomy

Topics: Animals; Carcinoma; Carcinoma 256, Walker; Chemistry, Pharmaceutical; Leukemia L1210; Melphalan; Mice; Nitrogen Mustard Compounds; Peptides; Pharmacology; Phenylalanine; Rats; Research; Sarcoma 180; Toxicology

Topics: Adenine Nucleotides; Adenosine Triphosphate; Animals; Carbohydrate Metabolism; Carcinoma; Carcinoma, Ehrlich Tumor; Female; Glucose; Humans; Melphalan; Metabolism; Ovarian Neoplasms; Oxidative Phosphorylation; Peptides; Pharmacology; Phosphorylation; Research; Sarcoma; Sarcoma, Experimental; Toxicology

Topics: Carcinoma; Female; Humans; Melphalan; Ovarian Neoplasms

Topics: Animals; Carcinoma; Carcinoma, Ehrlich Tumor; Cyclophosphamide; Cytostatic Agents; Mannomustine; Mechlorethamine; Melphalan; Metabolism; Mice; Neoplasms; Neoplasms, Experimental; Nitrogen Mustard Compounds; Phosphorus Isotopes; Radiation Injuries; Radiation Injuries, Experimental; Research; Triethylenemelamine

Topics: Aminopterin; Antineoplastic Agents; Carcinoma; Chemotherapy, Cancer, Regional Perfusion; Chlorambucil; Dactinomycin; Fibrosarcoma; Fluoresceins; Humans; Infusions, Parenteral; Injections, Intra-Arterial; Lymphoma; Lymphoma, Non-Hodgkin; Melanoma; Melphalan; Neoplasms; Pharmacology; Thiotepa; Toxicology

Topics: Animals; Carcinoma; Mechlorethamine; Melphalan; Nitrogen Mustard Compounds; Rats; Serum