melphalan and Carcinoma--Squamous-Cell

Topics: Adenocarcinoma, Mucinous; Altretamine; Antineoplastic Agents; Carcinoma, Squamous Cell; Cisplatin; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Female; Humans; Melphalan; Neoplasm Staging; Ovarian Neoplasms; Prognosis

Topics: Adult; Alkylating Agents; Antineoplastic Agents; Breast Neoplasms; Carcinoma, Bronchogenic; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Child; Cyclophosphamide; Doxorubicin; Drug Combinations; Drug Therapy, Combination; Female; Fluorouracil; Humans; Immunotherapy; Leucovorin; Male; Melphalan; Methotrexate; Neoplasm Metastasis; Neoplasms; Osteosarcoma; Prednisone; Rhabdomyosarcoma; Testicular Neoplasms; Thiotepa; Vinblastine; Vincristine

To report the 4-year outcomes of a consecutive series of anal cancer patients treated with concurrent chemo-radiation delivered with intensity-modulated radiotherapy (IMRT), employing a simultaneous integrated boost (SIB) approach.. A consecutive series of 54 patients was enrolled between 2007 and 2013. Treatment schedule consisted of 50.4 Gy/28 fractions (1.8 Gy daily) to the gross tumor volume, while the elective nodal volumes were prescribed 42 Gy/28 fractions (1.5 Gy/daily) for patients having a cT2N0 disease. Patients with cT3-T4/N0-N3 tumors were prescribed 54 (T3) or 60 (T4) Gy/30 fractions (1.8-2 Gy daily) to the gross tumor volume; gross nodal volumes were prescribed 50.4 Gy/30 fr (1.68 Gy daily) if sized ≤ 3 cm or 54 Gy/30 fr (1.8 Gy daily) if > 3 cm; elective nodal regions were given 45 Gy/30 fractions (1.5 Gy daily). Chemotherapy was administered concurrently according to the Nigro's regimen. Primary endpoint was colostomy-free survival (CFS). Secondary endpoints were local control (LC), disease-free survival (DFS), cancer-specific survival (CSS), overall survival (OS), and toxicity profile.. Median follow up was 32.6 months (range 12-84). The actuarial probability of being alive at 4 years without a colostomy (CFS) was 68.9% (95% CI: 50.3%-84.7%). Actuarial 4-year OS, CSS, DFS, and LC were 77.7% (95% CI: 60.7-88.1%), 81.5% (95% CI: 64%-91%), 65.5% (95% CI: 47.7%-78.5%), and 84.6% (95% CI: 71.6%-92%). Actuarial 4-year metastasis-free survival was 74.4% (95% CI: 55.5%-86.2%). Maximum detected acute toxicities were as follows: dermatologic -G3: 13%; GI-G3: 8%; GU-G3: 2%; anemia-G3: 2%; neutropenia-G3:11%; G4: 2%; thrombocytopenia- G3:2%. Four-year G2 chronic toxicity rates were 2.5% (95% CI: 3.6-16.4) for GU, 14.4% (95% CI: 7.1-28) for GI, 3.9% (95% CI: 1%-14.5%) for skin, and 4.2% (95% CI: 1.1-15.9) for genitalia.. Our study shows the feasibility of IMRT in the combined modality treatment of anal cancer, with comparable results to the literature with respect to LC, sphincter preservation and survival. Acute toxicity is lower if compared to series employing standard techniques. Our results support the use of IMRT on a routine basis for the treatment of anal cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Anus Neoplasms; Carcinoma, Squamous Cell; Chemoradiotherapy; Cyclophosphamide; Disease-Free Survival; Female; Fluorouracil; Humans; Kaplan-Meier Estimate; Male; Melphalan; Middle Aged; Proportional Hazards Models; Radiotherapy, Intensity-Modulated; Semustine

Hyperthermic isolated limb perfusion (HILP) with tumor necrosis factor alpha (TNF-alpha), interferon gamma, and melphalan has proved to be useful in the treatment of recurrent malignant melanoma and of locally advanced soft tissue sarcomas of the extremities.. To determine whether this modality is also effective in the treatment of locally advanced nonmelanoma skin tumors of the extremities.. Fifteen patients with locally advanced primary, recurrent, or metastatic skin tumors of the extremities (12 with squamous cell carcinoma and 3 with Merkel cell carcinoma) underwent HILP with TNF-alpha, interferon gamma, and melphalan. Six tumors were localized in the upper extremity (40%), and 9 in the lower extremity (60%). Treatment-related complications, limb salvage rate, local recurrence, and regional and distant metastases were scored during a median follow-up of 20 months.. After HILP, 9 patients (60%) showed a complete response (with histopathological confirmation). Four patients (27%) showed a partial response (with histopathological confirmation in 1 patient), and 2 patients (13%) showed no change (with histopathological confirmation in 1 patient and with clinical evidence in 1 patient). Two patients (13%) showed treatment-related complications. The limb salvage was achieved in 12 patients (80%), and the local recurrences developed in 4 patients (27%). During follow-up, regional lymph node metastases were observed in 2 patients (13%) and distant metastases in 2 patients (13%).. Based on our results, HILP with TNF-alpha, interferon gamma, and melphalan should be considered as a limb-saving treatment modality in patients with locally advanced nonmelanoma skin tumors of the extremities who would otherwise be candidates for ablative surgery.

Topics: Adult; Aged; Antineoplastic Agents; Arm; Carcinoma, Merkel Cell; Carcinoma, Squamous Cell; Chemotherapy, Cancer, Regional Perfusion; Female; Follow-Up Studies; Hot Temperature; Humans; Interferon-gamma; Leg; Male; Melphalan; Middle Aged; Skin Neoplasms; Tumor Necrosis Factor-alpha

Radiotherapy has been standard therapy for locally advanced squamous cell cervical cancer. Neoadjuvant chemotherapy is being studied to improve responses and survival. We report a phase II study in locally advanced squamous cell cervical cancer (FIGO stages III and IVA) using chemotherapy with bleomycin, methotrexate and cisplatin (BMP) followed by radical radiotherapy. Of the 35 patients, 31 in stage III and 4 in stage IVA, 3 complete responses (CR) and 22 partial responses (PR) were achieved after chemotherapy treatment. Thirty-one patients completed radiotherapy; 19 achieved CR and 4 PR. Five-year actuarial survival for the entire group was 45% (95% confidence interval, 37-53%) with a median survival of 56 months. Patients with CR had a significantly better survival: the 5-year actuarial survival was 74% (95% CI, 59-89%). Recurrence developed in 4 of 19 patients. The most frequent side-effects were nausea and vomiting. Myelosuppression and impaired renal function also occurred. There was no evidence of radiotherapy toxicity enhancement. The stage and Karnofsky index were significant prognostic factors. It is concluded that BMP chemotherapy in advanced cervical cancer is effective and, followed by radiotherapy, allows a good control of this tumor. The group of patients with complete response have a low rate of recurrences and a long survival chance.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Carmustine; Chemotherapy, Adjuvant; Disease-Free Survival; Female; Humans; Melphalan; Middle Aged; Prednisone; Survival Rate; Uterine Cervical Neoplasms

The matrix protein tenascin-C (TN-C) is present in the blood of healthy individuals at concentrations around 1 mg/l. Elevated serum levels have been reported in cancer patients. In this study we have measured the concentration of circulating TN-C in 40 patients with melanoma, soft-tissue sarcoma (STS) or squamous-cell carcinoma (SCC) of the limbs, and have found a minor increase in the mean concentration compared with healthy subjects. Only 10 patients had TN-C levels above the normal range. No correlation was observed between TN-C levels and tumor burden. Nineteen patients were treated by isolation limb perfusion (ILP) with TNF, IFN gamma, melphalan (11 melanoma, 2 SCC and I STS), melphalan alone (3 melanoma) or hyperthermia at 41.5 degrees C (2 melanoma). ILP with TNF, IFN gamma and melphalan induced a rapid increase in plasma TN-C levels, peaking in most patients between 24 or 48 hr after ILP. Two patients treated with hyperthermia only had a slow increase in TN-C concentration peaking at day 4, while the patients treated with melphalan alone had no significant change. In some cases elevated TN-C levels persisted for over 8 weeks after ILP. The early rise in TN-C concentration correlates with the increase in circulating C-reactive protein. Our findings suggest that circulating TN-C behaves, at least in part, as an acute-phase protein and that it may play a role in the inflammatory response.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Blood Platelets; C-Reactive Protein; Carcinoma, Squamous Cell; Chemical and Drug Induced Liver Injury; Chemotherapy, Cancer, Regional Perfusion; Dose-Response Relationship, Drug; Extremities; Female; Humans; Interferon-gamma; Interleukin-6; Male; Melanoma; Melphalan; Middle Aged; Neoplasms; Recombinant Proteins; Sarcoma; Soft Tissue Neoplasms; Tenascin; Tumor Necrosis Factor-alpha

The Illinois Cancer Center entered 25 patients on a phase II trial of intravenous melphalan treating patients with recurrent, metastatic or locally advanced and inoperable squamous cell carcinoma of the head and neck. All patients had bi-dimensionally measurable disease, at least a sixty day life expectancy, and adequate performance status (ECOG scale < or = 2). All patients except one had received prior radiotherapy, chemotherapy or both. Melphalan dosage was 30 mg/m2 every three weeks. Twenty-four patients were evaluable for response. One patient with laryngeal carcinoma had a clinical complete response of a nodal metastasis. Four patients had stabilization of disease for one to three months. There was formidable toxicity, including neutropenia (ANC < 1000/microliters 36%), and thrombocytopenia (< 50,000/microliter 32%). There were no drug-related deaths. Melphalan administered intravenously does not appear to be efficacious therapy in patients with previously treated advanced head and neck squamous carcinomas.

Topics: Adult; Aged; Bone Marrow; Carcinoma, Squamous Cell; Drug Evaluation; Female; Head and Neck Neoplasms; Humans; Injections, Intravenous; Leukocyte Count; Male; Melphalan; Middle Aged; Neutropenia; Survival Rate; Thrombocytopenia

Ninety-three women with FIGO stage II epithelial ovarian carcinoma underwent comprehensive surgical staging and were randomized prospectively to therapy consisting of either intraperitoneal radioactive phosphorus or oral melphalan. No patient had gross residual disease at the time of randomization. Ten of the forty-five women treated with melphalan experienced severe bone marrow depression at some time during therapy and two women expired from leukemia. Four of the forty-eight women treated with intraperitoneal phosphorus required surgical reexploration for intestinal obstruction or bowel injury. Twenty-one women died of their disease. Survival was not statistically different between the two treatment arms. The 5-year actuarial survival was 78%.

Topics: Adolescent; Adult; Aged; Ascites; Carcinoma, Squamous Cell; Child; Combined Modality Therapy; Female; Follow-Up Studies; Humans; Melphalan; Middle Aged; Neoplasm Staging; Ovarian Neoplasms

A small minority of patients present with locally advanced cutaneous Squamous Cell Carcinoma (cSCC). The aim of this study was to evaluate the effectiveness of Tumour necrosis factor α (TNF) and melphalan based isolated limb perfusion (TM-ILP) as a limb saving strategy for locally advanced extremity cSCC.. A retrospective search from prospectively maintained databases, at two tertiary referral centers, was performed to identify patients treated with TM-ILP for locally advanced cSSC of an extremity between 2000 and 2015.. A total of 30 patients treated with TM-ILP for cSCC were identified, with a median age of 71 years (36-92) and 50% female. Response could not be evaluated in 3 patients. After a median follow up of 25 months, the overall response rate was 81% (n = 22), with 16 patients having a complete response (CR, 59%). A total of 7 patients developed local recurrence, with a median time to recurrence of 9 months (Interquartile Range 7-10). Progressive disease was observed in 5 patients (19%). Limb salvage rate was 80%. The overall 2-year survival was 67%.. TM-ILP should be considered as an option in patients with locally advanced cSCC in specialised centers, resulting in a high limb salvage rate.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Female; Humans; Limb Salvage; Lower Extremity; Male; Melphalan; Middle Aged; Perfusion; Retrospective Studies; Skin Neoplasms; Survival Analysis; Tertiary Care Centers; Treatment Outcome; Tumor Necrosis Factor-alpha

Isolated limb perfusion (ILP) is an established and effective treatment for advanced melanoma and soft tissue sarcomas of the extremities with a high overall response rate. The aim of this study was to describe our experience of ILP for more rare types of tumours.. Patients with Merkel cell carcinoma (MCC) (n = 4), squamous cell carcinoma (SCC) (n = 2), B-cell lymphoma (n = 1), desmoid tumours (n = 3), pigmented villonodular synovitis (PVNS) (n = 1) and giant cell tumour (n = 1) were treated with ILP and analysed retrospectively.. The four patients with in-transit MCC had three complete responses (CR) and one partial response (PR); the two patients with SCC had one CR and one stable disease (SD); the patients with desmoid tumours had two PR and one SD. A CR was also observed for the patient with a giant cell tumour, but the patient with PVNS had a SD. The patient with cutaneous metastases of B-cell lymphoma showed a CR, however with rapid systemic progression. Local toxicity according to Wieberdink was grade II in 10 patients (83%) and grade III in two patients (17%).. These results show that ILP can be used as a treatment option also for more rare disease entities when other treatments have failed.

Topics: Abdominal Neoplasms; Adenomatous Polyposis Coli; Antineoplastic Agents, Alkylating; Carcinoma, Merkel Cell; Carcinoma, Squamous Cell; Chemotherapy, Cancer, Regional Perfusion; Extremities; Fibromatosis, Aggressive; Giant Cell Tumors; Humans; Hyperthermia, Induced; Lymphoma, B-Cell; Melphalan; Perfusion; Rare Diseases; Synovitis, Pigmented Villonodular; Tumor Necrosis Factor-alpha

Although studies of melphalan-based isolated limb infusion (ILI) combine data from upper extremity (UE) treatments with those from lower extremity (LE) treatments, differences between the 2 may be clinically important.. Candidates for UE ILI (n = 51) and LE ILI (n = 192) were identified from prospective databases at 2 institutions. The Response Evaluation Criteria in Solid Tumors and Wieberdink toxicity scale were used as appropriate.. The following patients had indications for UE ILI: melanoma, 36 of 47 patients (77%); sarcoma, 5 of 47 patients (11%); Merkel cell sarcoma, 3 of 47 patients (6%), and squamous cell carcinoma, 3 of 47 patients (6%). The patients who underwent UE ILI, as expected, had lower limb volumes (mean, 2.5 L vs 8.6 L; P < .001) and lower mean melphalan doses (20.7 mg vs 49.5 mg; P < .001). On perfusate blood gas analysis, the mean base excess at 30 minutes (-13.9 vs -9.1; P < .001) and the mean pH at 30 minutes (7.06 vs 7.15; P < .001) were lower for UE procedures than for LE procedures, although the mean ischemic time was longer in LE procedures (67.2 minutes) than in UE procedures (61.6 minutes; P = .03). The rate of regional toxicity grade ≥3 for UE ILI was 7% compared with 24% (P = .005) for LE ILI. There was no difference in the complete response rate for melanoma UE procedures (28%; 95% confidence interval, 16%-44%) compared with LE ILI procedures (32%; 95% confidence interval, 25%-39%).. ILI for UE disease was associated with similar complete response rates but lower toxicity than ILI for LE disease and with different physiologic sequelae despite comparable methods. The UE appears relatively resistant to toxic effects of melphalan-based ILI as currently performed, which suggests a potential for further optimization of drug dosing for UE ILI.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Alkylating; Carcinoma, Merkel Cell; Carcinoma, Squamous Cell; Chemotherapy, Cancer, Regional Perfusion; Extremities; Female; Follow-Up Studies; Humans; Lower Extremity; Male; Melanoma; Melphalan; Middle Aged; Prognosis; Prospective Studies; Sarcoma; Survival Rate; Upper Extremity; Young Adult

To demonstrate the efficacy of isolated limb infusion (ILI) in limb preservation for patients with locally advanced soft-tissue sarcomas and nonmelanoma cutaneous malignant neoplasms.. Locally advanced nonmelanoma cutaneous and soft-tissue malignant neoplasms, including soft-tissue sarcomas of the extremities, can pose significant treatment challenges. We report our experience, including responses and limb preservation rates, using ILI in cutaneous and soft-tissue malignant neoplasms.. We identified 22 patients with cutaneous and soft-tissue malignant neoplasms who underwent 26 ILIs with melphalan and dactinomycin from January 1, 2004, through December 31, 2009, from 5 institutions. Outcome measures included limb preservation and in-field response rates. Regional toxic effects were measured using the Wieberdink scale and serum creatinine phosphokinase levels.. The median age was 70 years (range, 19-92 years), and 12 patients (55%) were women. Fourteen patients (64%) had sarcomas, 7 (32%) had Merkel cell carcinoma, and 1 (5%) had squamous cell carcinoma. The median length of stay was 5.5 days (interquartile range, 4-8 days). Twenty-five of the 26 ILIs (96%) resulted in Wieberdink grade III or less toxicity, and 1 patient (4%) developed grade IV toxicity. The median serum creatinine phosphokinase level was 127 U/L for upper extremity ILIs and 93 U/L for lower extremity ILIs. Nineteen of 22 patients (86%) underwent successful limb preservation. The 3-month in-field response rate was 79% (21% complete and 58% partial), and the median follow-up was 8.6 months (range, 1-63 months). Five patients underwent resection of disease after an ILI, of whom 80% are disease free at a median of 8.6 months.. Isolated limb infusion provides an attractive alternative therapy for regional disease control and limb preservation in patients with limb-threatening cutaneous and soft-tissue malignant neoplasms. Short-term response rates appear encouraging, yet durability of response is unknown.

Topics: Adult; Aged; Aged, 80 and over; Antibiotics, Antineoplastic; Antineoplastic Agents, Alkylating; Biomarkers, Tumor; Carcinoma, Merkel Cell; Carcinoma, Squamous Cell; Chemotherapy, Cancer, Regional Perfusion; Creatine Kinase; Dactinomycin; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Length of Stay; Limb Salvage; Male; Melphalan; Middle Aged; Retrospective Studies; Sarcoma; Skin Neoplasms; Soft Tissue Neoplasms; Treatment Outcome; Young Adult

Topics: Anti-Inflammatory Agents; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Boronic Acids; Bortezomib; Carcinoma, Squamous Cell; Clarithromycin; Dexamethasone; Diphosphonates; Glomerulonephritis; Humans; Idarubicin; Imidazoles; Immunosuppressive Agents; Male; Melphalan; Middle Aged; Multiple Myeloma; Nephrotic Syndrome; Pamidronate; Protein Synthesis Inhibitors; Pyrazines; Skin Neoplasms; Thalidomide; Zoledronic Acid

Irradiation of human melanoma (MeWo, Be11) and squamous cell carcinoma (4451, 4197) cells induces cell cycle blocks from which the cells recover to re-enter mitosis after 40-60 h. In the TP53 mutant cell lines, MeWo and 4451, irradiation induces a G(2)-phase block, where the fraction of cells in G(2) phase reaches a maximum after 18-20 h. In the TP53 wild-type cell lines, 4197 and Be11, a G(1)- and G(2)-phase block is reached 12 and 16 h postirradiation, respectively. Addition of pentoxifylline after irradiation at the time when the number of cells in G(2) phase has reached a maximum shortens the normal recovery from G(2)-phase block to approximately 7 h. Addition of daunorubicin, melphalan and cisplatin under these conditions markedly enhanced drug toxicity. In the TP53-mutated cell lines MeWo and 4451, the survival ratio at 7 Gy measured by colony formation was 2.3-2.8, 8.6-85 and 52-74 for daunorubicin, melphalan and cisplatin, respectively. In the TP53 wild-type cell lines, the corresponding survival ratios were found to be 1.3-1.4, 2.3-3.0 and 1.2-2.6, respectively. The survival ratios are for clonogenic survival after 7 Gy and 2 mM pentoxifylline and measure the influence of drug doses that ensure 95% survival in nonirradiated controls. The results indicate that the G(2)-phase block is a crucial event in the damage response that can be manipulated to achieve a significant enhancement of drug toxicity. These effects are particularly pronounced in TP53 mutant cells and are observed at drug doses well below the clinical range.

Topics: Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cell Count; Cell Cycle; Cell Survival; Cisplatin; Daunorubicin; Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Flow Cytometry; G2 Phase; Humans; Melanoma; Melphalan; Mitosis; Mutation; Pentoxifylline; Tumor Cells, Cultured; Tumor Suppressor Protein p53

The authors review their experience of 4 years with isolated limb perfusion for the application of high dose TNF-alpha associated to IFN-gamma and melphalan for the treatment of regionally advanced tumours such as malignant melanoma, soft tissue sarcoma and epidermoid carcinoma. In malignant melanoma, the complete remission rate reaches 91%. In irresectable soft tissue sarcoma, this treatment when used as a neoadjuvant treatment saves the limb from amputation in 87.5% of the cases. Similar results are obtained for epidermoid carcinoma. With the regional application of high doses of TNF-alpha associated to chemotherapy and IFN-gamma, it has been possible to validate the concept of a strategy based on a dual targeting, that is the selective impact of the intratumoral vessels by TNF-alpha and of the tumour cells by chemotherapy. This approach appears to be the treatment of choice for locally advanced tumours of the limbs. However, as a single therapy, this procedure should be considered in melanoma as an induction therapy, and in sarcoma, as a preoperative treatment.

Topics: Antineoplastic Agents, Alkylating; Arm; Carcinoma, Squamous Cell; Chemotherapy, Cancer, Regional Perfusion; Drug Therapy, Combination; Follow-Up Studies; Humans; Interferon-gamma; Leg; Melphalan; Neoplasm Staging; Sarcoma, Clear Cell; Soft Tissue Neoplasms; Tumor Necrosis Factor-alpha

Four alpha-MSH drug conjugates have been synthesized, 2 C-terminal (Pep 3 and 4) and 2 central fragments (Pep 1 and 2), the latter being the 4-10 sequence known to be the main alpha-MSH-receptor-recognition site. Melphalan was introduced into each sequence at different locations. Their ability to recognize alpha-MSH receptors as well as their cytotoxic effects were compared in 3 cell lines: melanoma, carcinoma and fibroblast cells. Pep 1 and 2 were able to specifically bind to MSH receptors on melanoma cells by displacing labelled alpha-MSH from its binding sites at concentrations similar to the 4-10 heptapeptide sequence known to contain the main receptor-recognition site. They subsequently penetrate the cell, most probably by a receptor internalization mechanism, since about half of their effect could be inhibited by competition at the receptor level. Significant and selective cytotoxic effects to melanoma cells could be observed after only 2 hr exposure to the drug conjugates. Interestingly, these 2 conjugates, differing only in melphalan position, showed completely different cytotoxicity in terms of IC50 values, Pep 1 being 24 times more toxic to all cells; but the 2 were equally specific to melanoma cells. However, they both were less toxic to all cells than melphalan itself. Furthermore, Pep 1 and 2 were able to block the receptor and, unlike Pep 3 and 4, their cytotoxic effect could be significantly inhibited by an alpha-MSH agonist. Pep 3 and 4 were 5 to 10 times less toxic than melphalan to melanoma and carcinoma cells and 50 times less to fibroblast cells, and did not show any cell-type selectivity. They were less toxic than Pep 1 to melanoma and carcinoma cells by a factor of 2, but equally toxic to fibroblasts. In contrast, they were more toxic than Pep 2 to fibroblasts, melanoma and carcinoma by a factor of 3, 10 and 24 respectively. Our data strongly suggest a receptor-mediated cytotoxicity mechanism occurring with alpha-MSH central fragments in human melanoma cells due to the presence of alpha-MSH-specific receptors. This mechanism appeared to be both peptide- and cell-type-specific.

Topics: alpha-MSH; Carcinoma, Squamous Cell; Cells, Cultured; Drug Combinations; Drug Screening Assays, Antitumor; Fibroblasts; Humans; Melanoma; Melphalan; Molecular Sequence Data; Receptors, Pituitary Hormone; Skin Neoplasms; Structure-Activity Relationship; Tumor Cells, Cultured

Topics: Bone Neoplasms; Carcinoma, Squamous Cell; Chemotherapy, Cancer, Regional Perfusion; Drug Monitoring; Drug Therapy, Combination; Female; Hemodynamics; Humans; Interleukins; Melphalan; Middle Aged; Soft Tissue Neoplasms; Tibia; Time Factors; Tumor Necrosis Factor-alpha

Dietary levels of beta-carotene and vitamin E have been associated with cancer prevention and to a lesser extent, with therapeutic enhancement of cancer treatment. We report on the cytotoxicity of beta-carotene, vitamin E, and the combination of beta-carotene and vitamin E in human SCC-25 squamous carcinoma cells under various environmental conditions found in solid tumor masses. Beta-Carotene was selectively cytotoxic toward normally oxygenated cells and was generally more cytotoxic at normal pH than at acidic pH (6.45). Vitamin E was selectively cytotoxic toward normally oxygenated cells following 6 h exposure at normal pH and was generally equally cytotoxic toward normally oxygenated and hypoxic cells under the other conditions tested. Beta-Carotene was an effective modulator of cisplatin (CDDP) cytotoxicity toward SCC-25 cells, whereas vitamin E was not. Both beta-carotene and vitamin E were effective modulators of melphalan cytotoxicity toward SCC-25 cells. Treatment of SCC-25 cells with beta-carotene (70 microM, 2h) resulted in a reduction in superoxide dismutase activity, in glutathione-S-transferase activity, and in nonprotein sulfhydryl levels in the cells. Exposure to vitamin E or to a combination of beta-carotene and vitamin E increased the glutathione-S-transferase activity in SCC-25 cells by 40%-45% over the control value. Treatment with beta-carotene, vitamin E, or canthaxanthin reduced the incorporation of [3H]-thymidine into SCC-25 cells but not that into normal human keratinocytes. The most marked reduction in [3H]-thymidine incorporation into SCC-25 cells occurred following treatment with the combination of beta-carotene and melphalan. We hope to continue to explore the mechanisms of this effect and to study these combinations in vivo.

Topics: Alkylating Agents; Antineoplastic Agents; beta Carotene; Carcinoma, Squamous Cell; Carotenoids; Cell Hypoxia; Cell Survival; Dose-Response Relationship, Drug; Drug Interactions; Humans; Hydrogen-Ion Concentration; Melphalan; Organoplatinum Compounds; Tumor Cells, Cultured; Vitamin E

Alkylating agents have been used individually and in combination to treat epithelial ovarian carcinoma. In this study, the cytotoxicity of 7 alkylating agents has been measured using a serial dilution clonogenic assay. When individual agents were evaluated, markedly different activity was observed against several ovarian cancer cell lines. Among 4 cell lines tested, OVCA 432 was the most sensitive to cisplatin, thiotepa and melphalan. When alkylating agents were used in combination against OVCA 432, synergistic activity was observed with cisplatin and each of several other alkylating agents including thiotepa, melphalan, 4-hydroperoxycyclophosphamide (4HC) and carboplatin. The combination of cisplatin and thiotepa also exerted synergistic activity against the OVCA 420, 429 and 433 cell lines, but had only additive or subadditive activity against the NIH:OVCAR-3 cell line. Sequential treatment of tumor cell lines with the different alkylating agents was as effective as simultaneous treatment. Synergistic anti-tumor activity in cell culture is consistent with clinical observations that alkylating agents in combination appear more effective than single agents for treatment of advanced epithelial ovarian cancer. In addition, our study suggests that cisplatin in combination with thiotepa, 4HC or melphalan might prove useful for high-dose therapy with autologous bone-marrow support.

Topics: Alkylating Agents; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Squamous Cell; Cell Division; Cisplatin; Cyclophosphamide; Drug Synergism; Female; Humans; Melphalan; Ovarian Neoplasms; Thiotepa; Tumor Cells, Cultured

236 patients with various advanced malignant solid tumors treated by combined chemotherapy with routine doses of cisplatin (DDP) from 1980 to 1986 are presented. According to different doses of cisplatin everyday, the patients were divided into 4 groups: 1. 20 mg/day x4-5, 80 cases; 2. 30 mg/day x3-5, 91 cases; 3. 40 mg/day x3-4, 37 cases; 4. 50 mg/day x2-3, 28 cases. Each group was repeated for 3 weeks. The effect and toxicity were analysed and compared with 22 cases treated by single DDP in 1975. The response (CR + PR) rate was 39.2% in 194 evaluated patients. The response rate was similar in group 20 mg and single DDP (29.2% and 27.3%). The response rate was lower than that of group 30 mg, 40 mg, and 50 mg (43.4%, 42.4%, and 50%) (P less than 0.05). The remissions in various groups were not significantly different. The toxicity of combined chemotherapy was not severe. 91.1% of patients had nausea and vomiting. There was no statistical difference in the various groups. Bone marrow suppression was less in single DDP group than that of combined chemotherapy group, (P less than 0.05). DDP 30 mg-50 mg 1/d x5-3 was better than HD-DDP in some patients.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Carcinoma, Squamous Cell; Cisplatin; Female; Fluorouracil; Humans; Lomustine; Lung Neoplasms; Male; Melanoma; Melphalan; Methotrexate; Middle Aged; Neoplasms; Procarbazine; Testicular Neoplasms; Vincristine

Between 1975 and 1984, 33 patients with squamous cell carcinoma of the nasopharynx received adjuvant chemotherapy before and/or after definitive radiotherapy at UT M. D. Anderson Hospital. The favored chemotherapy regimens during this time were BCMF (bleomycin, cyclophosphamide, methotrexate, and 5-FU) and PMB (cisplatinum, methotrexate, and bleomycin). Total radiation doses to the primary site averaged 65 Gy for T1 and T2 lesions and 70 Gy for T3 and T4 lesions. Neck nodes were given boost treatments to a maximum of 70 Gy, depending on the extent of the disease. The outcome of treatment in these patients was compared to that of a stage-matched group of 71 patients treated during the same time period with radiotherapy alone. However, the groups were not matched with regard to histologic subtypes: 45% of the radiation-only group had prognostically unfavorable keratinizing squamous carcinomas (WHO 1) compared with 18% of the combined modality group. Overall disease-free survival at 5 years was 63% in the combined modality group and 44% in the radiation only group (p = 0.15). Both acute reactions and late treatment complications were much more frequent and severe in patients receiving combined modality treatment. In patients treated with chemotherapy prior to radiation therapy, 10/20 (50%) experienced severe acute toxicity (RTOG Grade 3 or 4) versus 9/71 (13%) in the radiotherapy-only group. Severe late normal tissue injury occurred in 15/33 (45%) of the combined modality group versus 5/71 (7.0%) in the control group. The majority of the late complications in the adjuvant chemotherapy group consisted of severe soft tissue and muscle fibrosis. The average total bleomycin dose in the patients with severe late soft tissue and muscle fibrosis was 336 mg. The actuarial risk of developing a severe late complication by 2 years after treatment was 68% in the combined modality group versus 8% in the radiation-therapy-only group (p = .001). The probability of remaining both disease-free and complication-free at 5 years was 40% in the radiation-only group and 22% in the combined-modality group (p = 0.08). Comparison of these results with other published reports emphasizes the importance of late toxicity data in assessing the ultimate value of combined modality therapy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Fluorouracil; Follow-Up Studies; Humans; Melphalan; Methotrexate; Nasopharyngeal Neoplasms; Neoplasm Staging; Prognosis; Radiotherapy Dosage

The tourniquet infusion method was compared with hyperthermic perfusion in canine limbs by using Adriamycin, actinomycin-D, and melphalan. Tourniquet infusion provided comparable tissue levels with Adriamycin and significantly higher levels with actinomycin-D and melphalan in the treated extremity than hyperthermic perfusion with the same drugs and dosages. Higher systemic leak was observed, more so with melphalan, with the tourniquet infusion method. Tourniquet infusion has caused complete regression of four malignant tumors involving extremities (one malignant melanoma, two Kaposi's sarcomas, one squamous cell carcinoma) and partial greater than 50% regression of nine tumors (three malignant melanomas, three squamous cell carcinomas, one malignant schwannoma, one malignant fibrohistiocytoma, one liposarcoma) followed by excision of residual tumor. Five patients with extremity sarcomas precluding adequate surgical margins were treated preoperatively with the this method. Longer follow-up is needed, as is a larger number of patients for a valid comparison of tourniquet infusion with hyperthermic perfusion.

Topics: Aged; Animals; Antineoplastic Agents; Carcinoma, Squamous Cell; Chemotherapy, Cancer, Regional Perfusion; Dactinomycin; Dogs; Doxorubicin; Extremities; Female; Hindlimb; Humans; Infusions, Intra-Arterial; Male; Melanoma; Melphalan; Middle Aged; Sarcoma; Skin Neoplasms; Tissue Distribution; Tourniquets

The authors report the results of clinical elaboration and testing of the technic of intraesophageal intratumor sarcolysin iontophoresis associated with radiotherapy in 40 inoperable patients with cancer of the thoracic esophagus. A total focal dose of irradiation was on the average 1/3 less compared with the routine one. Iontophoresis was performed by a specially designed electrode with 5-10 mA during 60 minutes. The iontophoresis procedure was followed by irradiation. The immediate good results of the treatment were twice as frequent as in control groups. The treatment proceeded with less pronounced radiation response. An average survival of patients while using chemical drugs intophoresis proved to be equal to control data that is likely to be due to the far-advanced stage of the disease in most patients. An average survival in patients with less tumor proliferation was found to be longer than in analogous control series.

Topics: Adult; Antineoplastic Agents; Carcinoma, Basal Cell; Carcinoma, Papillary; Carcinoma, Squamous Cell; Demecolcine; Drug Therapy, Combination; Esophageal Neoplasms; Evaluation Studies as Topic; Female; Humans; Iontophoresis; Male; Melphalan; Middle Aged; Radiotherapy Dosage; Time Factors

Topics: Adenocarcinoma; Bleomycin; Carcinoma, Squamous Cell; Castration; Dactinomycin; Estrogens; Female; Humans; Kidney Neoplasms; Male; Melphalan; Nitrosourea Compounds; Phosphorus Isotopes; Plicamycin; Prostatic Neoplasms; Testicular Neoplasms; Urinary Bladder Neoplasms; Urogenital Neoplasms; Vinblastine; Vincristine

Topics: Adenocarcinoma; Alkylating Agents; Animals; Antibodies, Neoplasm; Antibody Formation; Antibody Specificity; Carcinoma 256, Walker; Carcinoma, Squamous Cell; Carrier Proteins; Colonic Neoplasms; Esophageal Neoplasms; Haptens; Hemagglutination Tests; Humans; Immune Sera; Immunization; Immunodiffusion; Immunoelectrophoresis; Melphalan; Rabbits; Rats; Species Specificity

Topics: Aged; Carcinoma, Squamous Cell; Female; Humans; Lung Neoplasms; Melphalan; Middle Aged; Pulmonary Artery; Pulmonary Fibrosis; Pulmonary Veins; Recurrence; Vascular Diseases

Topics: Acetazolamide; Animals; Antineoplastic Agents; Carcinoma, Squamous Cell; Diuretics; Female; Furosemide; Male; Melphalan; Mercaptopurine; Mice; Neoplasm Transplantation; Neoplasms, Experimental; Phosphines; Rats; Sarcoma 180; Sarcoma, Experimental; Serotonin

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

Topics: Adolescent; Adult; Aged; Bone Neoplasms; Carcinoma, Squamous Cell; Chemotherapy, Cancer, Regional Perfusion; Child; Extremities; Female; Hemorrhage; Humans; Hypotension; Leukopenia; Lymph Node Excision; Lymphoma, Large B-Cell, Diffuse; Male; Melanoma; Melphalan; Methods; Middle Aged; Postoperative Complications; Sarcoma; Skin Neoplasms

Topics: Adolescent; Adult; Antibiotics, Antineoplastic; Carcinoma, Squamous Cell; Chlorpromazine; Cyclophosphamide; Female; Fever; Humans; Liver Neoplasms; Lymphatic Metastasis; Lymphoma, Large B-Cell, Diffuse; Male; Mechlorethamine; Melphalan; Middle Aged; Nasopharyngeal Neoplasms; Nausea; Neoplasm Recurrence, Local; Olivomycins; Thiotepa; Thrombocytopenia; Tonsillar Neoplasms; Vomiting

Topics: Carcinoma, Squamous Cell; Diagnosis, Differential; Esophageal Neoplasms; Esophagus; Gastroenterostomy; Gastrostomy; Hematemesis; Humans; Male; Melphalan; Middle Aged; Neoplasm Metastasis; Neoplasms, Nerve Tissue; Pyloric Stenosis; Radiography; Vagotomy; Vagus Nerve

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Adenocarcinoma, Scirrhous; Antibiotics, Antineoplastic; Antineoplastic Agents; Breast Neoplasms; Carcinoma, Squamous Cell; Culture Techniques; Flavonoids; Fluorouracil; HeLa Cells; Humans; Lung Neoplasms; Melphalan; Mercaptopurine; Methods; Mitomycins; Neoplasms; Rectal Neoplasms; Stomach Neoplasms

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Agents; Carcinoma, Squamous Cell; Cyclophosphamide; Female; Fluorouracil; Humans; Hydroxyurea; Mechlorethamine; Melphalan; Methotrexate; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Progestins; Thiotepa; Urea; Uterine Cervical 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: Amputation, Surgical; Carcinoma, Squamous Cell; Chemotherapy, Cancer, Regional Perfusion; Extremities; Humans; Lymph Node Excision; Melanoma; Melphalan; Osteosarcoma; Sarcoma; Thiotepa

Topics: Aged; Carcinoma, Squamous Cell; Chemotherapy, Cancer, Regional Perfusion; Female; Hand; Humans; Leg; Male; Melphalan; Neoplasms

Topics: Antimetabolites; Antineoplastic Agents; Carcinoma, Squamous Cell; Chemotherapy, Cancer, Regional Perfusion; Dactinomycin; Geriatrics; Head and Neck Neoplasms; Humans; Infusions, Parenteral; Melanoma; Melphalan; Methotrexate; Mouth Neoplasms; Neoplasms; Neoplasms, Muscle Tissue; Nitrogen Mustard Compounds; Sarcoma; Toxicology; Triethylenemelamine